HYPERTENSION COMPENDIUM Hypertension in Low-and Middle-Income Countries

Abstract

In recent decades low-and middle-income countries (LMICs) have been witnessing a significant shift toward raised blood pressure; yet in LMICs, only 1 in 3 are aware of their hypertension status, and ≈8% have their blood pressure controlled. This rising burden widens the inequality gap, contributes to massive economic hardships of patients and carers, and increases costs to the health system, facing challenges such as low physician-to-patient ratios and lack of access to medicines. Established risk factors include unhealthy diet (high salt and low fruit and vegetable intake), physical inactivity, tobacco and alcohol use, and obesity. Emerging risk factors include pollution (air, water, noise, and light), urbanization, and a loss of green space. Risk factors that require further in-depth research are low birth weight and social and commercial determinants of health. Global actions include the HEARTS technical package and the push for universal health care. Promising research efforts highlight that successful interventions are feasible in LMICs. These include creation of health-promoting environments by introducing salt-reduction policies and sugar and alcohol tax; implementing cost-effective screening and simplified treatment protocols to mitigate treatment inertia; pooled procurement of low-cost single-pill combination therapy to improve adherence; increasing access to telehealth and mHealth (mobile health); and training health care staff, including community health workers, to strengthen team-based care. As the blood pressure trajectory continues creeping upward in LMICs, contextual research on effective, safe, and cost-effective interventions is urgent. New emergent risk factors require novel solutions. Lowering blood pressure in LMICs requires urgent global political and scientific priority and action.

Full text

Circulation Research is available at www.ahajournals.org/journal/res
Circulation Research
808 April 2, 2021 Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729
Correspondence to: Aletta E. Schutte, PhD, School of Population Health, University of New South Wales Sydney, Kensington Campus, Samuels Bldg, NSW 2052,
Australia. Email a.schutte@unsw.edu.au
The Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/CIRCRESAHA.120.318729.
For Disclosures, see page 822.
© 2021 American Heart Association, Inc.
HYPERTENSION COMPENDIUM
Hypertension in Low- and Middle-Income
Countries
Aletta E. Schutte , Nikhil Srinivasapura Venkateshmurthy , Sailesh Mohan, Dorairaj Prabhakaran
ABSTRACT: In recent decades low- and middle-income countries (LMICs) have been witnessing a significant shift toward
raised blood pressure; yet in LMICs, only 1 in 3 are aware of their hypertension status, and ≈8% have their blood pressure
controlled. This rising burden widens the inequality gap, contributes to massive economic hardships of patients and carers,
and increases costs to the health system, facing challenges such as low physician-to-patient ratios and lack of access to
medicines. Established risk factors include unhealthy diet (high salt and low fruit and vegetable intake), physical inactivity,
tobacco and alcohol use, and obesity. Emerging risk factors include pollution (air, water, noise, and light), urbanization, and
a loss of green space. Risk factors that require further in-depth research are low birth weight and social and commercial
determinants of health. Global actions include the HEARTS technical package and the push for universal health care. Promising
research efforts highlight that successful interventions are feasible in LMICs. These include creation of health-promoting
environments by introducing salt-reduction policies and sugar and alcohol tax; implementing cost-effective screening and
simplified treatment protocols to mitigate treatment inertia; pooled procurement of low-cost single-pill combination therapy
to improve adherence; increasing access to telehealth and mHealth (mobile health); and training health care staff, including
community health workers, to strengthen team-based care. As the blood pressure trajectory continues creeping upward in
LMICs, contextual research on effective, safe, and cost-effective interventions is urgent. New emergent risk factors require
novel solutions. Lowering blood pressure in LMICs requires urgent global political and scientific priority and action.
Key Words: developing countries ◼ diet ◼ epidemiology ◼ lifestyle ◼ risk factors
The increasing burden of hypertension and its dev-
astating consequences have come into focus only
recently. We have come a long way from masterly
inactivity as proposed by the physician of Franklin D.
Roosevelt to the current aggressive management of
hypertension as proposed by the American guidelines1
based on the SPRINT (Systolic Blood Pressure Inter-
vention Trial) results. Today, noncommunicable diseases
(NCDs) such as cardiovascular disease (CVD), diabetes,
cancers, and chronic respiratory disease are the lead-
ing cause of preventable disease, death, and disability,
accounting for three-quarters of the 56.5 million deaths
globally from all causes in 2019.2 Nearly one-third (18.6
million) of these deaths in 2019 were due to CVD. The
leading risk factor is raised blood pressure (BP) or
hypertension, which accounted for 10.8 million deaths
(19.2% of all deaths in 2019) and 9.3% of disability-
adjusted life-years lost globally.3,4
There are many consequences of raised BP. A
20-mm Hg increase in systolic BP (SBP) is associated
with a 35% greater risk for ischemic stroke (95% CI,
1.28–1.42), 29% greater risk for myocardial infarction
(95% CI, 1.25–1.34), and a 10-mm Hg increase in dia-
stolic BP with 45% increased risk for abdominal aortic
aneurism (95% CI, 1.34–1.56).5 A 20/10-mm Hg eleva-
tion from 120/80 mm Hg increases the adjusted rela-
tive risk of developing end-stage renal disease 2.6-fold.6
Midlife and late-life hypertension is also associated with
a 41% to 62% increased risk of incident dementia.7
Over the past 3 decades, raised BP has transi-
tioned from a significant burden in high-income coun-
tries (HICs) to one that is now highly prominent in
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729 April 2, 2021 809
Schutte et al Hypertension in LMICs
low- and middle-income countries (LMICs) including
South and East Asia and Sub-Saharan Africa. This
is evident from figures in 2015, where 23% of the
1.13 billion adults with raised BP lived in South Asia
(199 million in India) and another 21% (235 million)
in East Asia.8 Uncontrolled hypertension is higher in
LMICs compared with HICs.9–12 It has not only sev-
eral implications for the health of affected individuals
and resource-constrained health systems in LMICs
but also has substantial societal, developmental, and
economic costs.
In this review, we report the epidemiology and burden
of hypertension in LMICs according to the World Bank
regions. Further, we examine the specific features and
challenges in LMICs regarding the etiology, prevention,
and management of hypertension. We also highlight the
current research gaps and suggest key recommenda-
tions that can potentially help address the rising burden
of uncontrolled hypertension in LMICs.
EPIDEMIOLOGY AND BURDEN OF
DISEASE IN LMICS
Mortality and Disability
The prevalence of hypertension is increasing rapidly in
many LMICs that are undergoing diverse health transi-
tions. Using the GBD study (Global Burden of Disease)
data, we examined the epidemiology and burden as per
the World Bank classification of the world according to
income levels. In 2019, the highest age-standardized
death rates from CVD and SBP were reported from lower-
middle-income and low-income countries (Table 1).
The deaths attributable to high SBP were the highest
in the Middle East and North Africa and Sub-Saharan
regions when compared with North America (Table I in
the Data Supplement). In terms of disability-adjusted
life-years lost, years lived with disability, and years of life
lost, it was highest in upper middle-income countries
(Table II in the Data Supplement). disability-adjusted life-
years and years of life lost were the highest in Europe
and Central Asian Regions while East Asia and Pacific
Region had the highest loss in years lived with disabil-
ity. When looking at changes in these 3 indices between
1990 and 2019, increases were observed in upper
middle- and lower middle-income countries, whereas in
HICs, it decreased. During this period, disability-adjusted
life-years, years lived with disability, and years of life lost
increased in all regions except in North America and
European Regions (Figure 1).
Prevalence
A third of all adults are estimated to have hypertension,
which translates to about 1.4 billion adults. Population-
based reports on hypertension estimates are available
for many LMICs, but an expansion of high-quality stud-
ies that accurately measure BP from LMICs are encour-
aged.13 The GBD Study (which undertakes estimation of
risk factors by sophisticated statistical modeling tech-
niques including available large-scale national household
surveys, population-level surveys provided by collabo-
rators, programme-level data from government agen-
cies, and systematic reviews of epidemiological studies)
obtained a summary measure of exposure for each risk,
called the summary exposure value (SEV).14 The SEV
is a metric that captures risk-weighted exposure for a
population or risk-weighted prevalence of an exposure.
The scale for SEV spans from 0% to 100%, with a SEV
of 0% reflecting no risk exposure in a population and
100% indicating that an entire population is exposed to
the maximum possible risk. In the absence of adequate
national prevalence data on trends, this provides an indi-
cation of the likely burden of the risk factors or expo-
sure to them in a population. Figure 2 shows the SEVs of
the past 3 decades in the different World Bank regions
and indicates an increasing trend in high SBP in several
regions, especially in Sub-Saharan Africa, the Middle East
and North Africa, East Asia, and the Pacific. Apart from
the GBD data, a recent study that pooled data from 44
LMICs (1 100 507 participants) showed the prevalence
of hypertension to be 17%.15 The 2019 May Measure-
ment Month campaign (1 508 130 screenees) reported
that 34% had hypertension. Among those screened,
29.3% had hypertension in the South Asia region, while
Nonstandard Abbreviations and Acronyms
ACE angiotensin-converting enzyme
aOR adjusted odds ratio
BP blood pressure
COVID-19 coronavirus disease 2019
CVD Cardiovascular Disease
GBD Global Burden of Disease
HIC high-income country
ISH International Society of Hypertension
LMIC low- and middle-income country
NCD noncommunicable disease
OR odds ratio
PURE Prospective Urban Rural Epidemiology
SBP systolic blood pressure
SEV summary exposure value
SPRINT Systolic Blood Pressure Intervention Trial
TIPS-3 The International Polycap Study 3
TRIUMPH Triple Pill Versus Usual Care Manage-
ment for Patients With Mild-to-Moder-
ate Hypertension
UHC universal health coverage
WHO World Health Organization
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
810 April 2, 2021 Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729
Schutte et al Hypertension in LMICs
corresponding numbers in East Asia and Sub-Saharan
Africa were 30.6% and 27.9%, respectively.9
ETIOLOGY AND PATHOPHYSIOLOGY—
SPECIFIC FEATURES AND CHALLENGES
IN LMICS
Diet and Physical Activity
A total of 27 dietary factors have been identified, which
either increase the risk of developing hypertension or
are protective.16 Some prominent factors are sodium,
potassium, fruits and vegetables, and alcohol.16 The con-
sumption of healthy and unhealthy diets var substantially
between LMICs and HICs and also according to cultures
and geographies.
There is an exceptionally strong relation between
unhealthy diets and income, with low-income countries
having the highest score for consumption of unhealthy
diet compared with HICs (76 versus 46).17 The afford-
ability and availability of healthy foods such as fruits, veg-
etables, and nuts may explain some of these trends. A
cost analysis of affordability for the EAT-Lancet healthy
planetary diet shows that the proportion of mean daily
household income per capita spent was 6% for HIC. By
contrast, it was 28%, 52%, and 89% for upper middle,
lower middle, and low-income countries.18 These findings
reflect the higher costs of consuming healthier diets and
how low socioeconomic status likely limits the adoption
of healthy dietary behaviors that are necessary for the
prevention and control of hypertension.
The positive relationship between a high-salt diet and
hypertension has been confirmed by multiple observa-
tional studies, trials, and meta-analyses.19 As a result,
several health organizations, including the World Health
Organization (WHO), recommend restricting intake to <5
g/d. A meta-analysis reported that a reduction of ≈4.5
g of salt per day was associated with a decrease of 4.9
mm Hg of SBP and 2.7 mm Hg of diastolic BP among
patients with hypertension as compared with 2.0 and 1.0
mm Hg, respectively, among people with no hyperten-
sion.20 Food items like bread, meat and meat products,
milk and dairy products, instant noodles, condiments,
salted preserved foods, and bakery products contribute to
high-salt diets in LMICs.21 Low potassium intake, through
inadequate consumption of fruits and vegetables, is also
a major cause of high BP.22,23
Many hypertension treatment guidelines recommend
regular physical activity to reduce BP. Yoga has also
been found effective in reducing BP among patients
with hypertension24 and is recommended in the 2020
International Society of Hypertension (ISH) Hyperten-
sion Guidelines.25 It is understood that practicing yoga
and meditation may contribute to improved autonomic
balance leading to a reduction in BP.26
Over the past decades, abundant epidemiologi-
cal studies have confirmed that several elements of a
healthy lifestyle and behaviors are related to BP lower-
ing, as summarized in Table 2.
Tobacco and Alcohol
Tobacco kills >8 million people a year, with the stark real-
ity that over 80% of all tobacco users live in LMICs.35
With declining rates of tobacco consumption in HICs,
the tobacco industry is shifting its focus to LMICs tar-
geting the growing number of adolescents.36 Tobacco
and hypertension are independent risk factors for CVD.
However, the link between tobacco and hypertension is
unclear. Most of the evidence of tobacco and hyperten-
sion linkage is from smoking cigarettes. Tobacco use
should be discouraged to reduce the absolute risk for
vascular mortality among those with hypertension.
Alcohol is one of the most frequently abused sub-
stances worldwide. Though the prevalence of current
alcohol drinkers is high in HICs (67.3%) compared with
upper middle (47.4%), lower middle (30.1%), and low-
income (26.8%) countries, the prevalence of heavy
episodic drinking is high in low-income (45.4%) and
upper-middle-income (40.7%) and similar in lower-mid-
dle-income (37.7%) countries, as compared with HICs
(38.7%).37 Recent evidence from the GBD study shows
there is no safe level of alcohol drinking.38
Obesity
LMICs are facing a double burden of malnutrition,
namely the coexistence of undernutrition and overweight
Table 1. Age-Standardized Deaths (per 100 000 With 95% CIs) Due to CVD, High SBP, and High Sodium In-
take According to World Bank Income Classification of Countries in 2019
World Bank income classification of countries
High income
Upper middle
income
Lower middle
income Low income
Deaths due to CVD 133 (118–142) 267 (24–283) 313 (287–337) 304 (270–340)
CVD deaths due to high SBP 64 (54–74) 143 (121–164) 172 (149–197) 167 (142–192)
Deaths due to high SBP 72 (61–83) 153 (131–175) 187 (162–213) 184 (157–211)
Deaths due to diet high in sodium 9 (1–24) 35 (11–69) 22 (3–58) 26 (3–71)
CVD indicates cardiovascular disease; and SBP, systolic blood pressure.
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729 April 2, 2021 811
Schutte et al Hypertension in LMICs
or obesity.39 Nearly half of the world’s 671 million obese
population lives in 10 countries, of which 6 are LMICs.
India and China together contribute to 15% of the global
obese population, despite a low prevalence of obe-
sity.40 Obesity, defined as body mass index ≥30 kg/m2,
is an important risk factor for CVD, exerting detrimental
effects through several mechanisms.41 Obesity may also
lead to the development of chronic kidney disease, which
in turn increases BP and hampers efforts to control BP
among those with hypertension.42
Social and Commercial Determinants of Health
Social determinants include the causes of the causes of
health inequality. These are the unequal conditions in
which people are born, grow, live, work, and age. These
unequal conditions depend on a person’s socioeconomic
status, sex, ethnicity, and disability.43 Social determinants
influence the distribution of risk factors for hypertension,
such as unhealthy diets, physical inactivity, and tobacco
and alcohol consumption. People in the low socioeco-
nomic groups in LMICs are more likely to consume
unhealthy diets and use tobacco and alcohol.44 People in
poor neighborhoods are also more likely to be exposed
to air pollution45—an emerging risk factor for hyperten-
sion. Once diagnosed with hypertension, people with low
socioeconomic status are less likely to afford out-of-
pocket expenses for antihypertensive medication, lead-
ing to uncontrolled hypertension and early development
of complications. The interplay between poverty and
NCDs (which includes CVD, for which hypertension is an
important risk factor)46 is depicted in Figure 3.
More recently, it has also been established that
unhealthy behaviors are often influenced by commer-
cial determinants of health, namely “strategies and
approaches used by the private sector or select industries
Figure 1. Percentage change in deaths, disability-adjusted life-years (DALYs), years lived with disability (YLDs), and years of life
lost (YLLs) due to high systolic blood pressure according to the World Bank income classification of countries between 1990
and 2019.
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
812 April 2, 2021 Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729
Schutte et al Hypertension in LMICs
to promote products and choices that are detrimental to
health.”47 Large corporations selling unhealthy foods and
tobacco often target consumers including children, pub-
lic health professionals and organizations, researchers
and research organizations, civil society, national govern-
ments, and even United Nations through their activities
and earn profits at the expense of the health of indi-
viduals and societies. One example of such an activity
is the sponsorship of sporting events.48 Thus, a whole
systems approach is needed to tackle the causes of the
causes and a lifecourse approach to address such social
inequalities and vested commercial determinants.49
Green Space, Pollution, and Urbanization
Environmental factors such as green space (eg, the
amount of tree canopy), pollution, and urbanization are
strongly associated with raised BP. Between 2001 and
2018, LMICs have had the most extensive urban expan-
sion and the highest urban population growth compared
with HIC.50 Air pollution is 17× greater in cities of LMICs
compared with that in North America and Europe.51 The
urban poor are disproportionately affected by air pollution
as they live closer to industries and air-polluting activities.52
The prevalence of hypertension among people exposed
to >30% green space was 1.9 percentage points lower
compared with those who were exposed to 0% to 4%
green space. One percent increase in the amount of tree
canopy was associated with lower odds of incident hyper-
tension.53 The effect of green space on hypertension can
be explained by a multitude of factors that need to be
considered in urban health planning in rapidly growing
metropolitan areas in LMICs. Green space reduces expo-
sure to environmental stressors such as air pollution, heat,
and noise. It further enables physical activity and mental
health and encourages social interaction and cohesion.54
Environmental pollution is becoming an increasingly
important risk factor for hypertension, including water,
noise,55 light, and notably air pollution. Polluted air con-
tains particulate matter of different sizes, of which PM2.5 is
particularly important. The particulate matter in the lungs
leads to pulmonary oxidative stress and inflammation ini-
tiated by the release of cytokines, activated immune cells,
and vasoactive molecules.56 The soluble constituents in
the inhaled polluted air can cross the alveolar membrane
reaching the bloodstream and directly affecting the
vascular endothelium resulting in vasoconstriction and
arterial stiffness.57 Particulate matter can also stimulate
the autonomic nervous system resulting in sympathetic
nervous system–mediated arterial vasoconstriction.58
A recent study from India showed that for each inter-
quartile range increase in monthly PM2.5 exposure, SBP
increased by 1.8 mm Hg and diastolic BP increased by
1.1 mm Hg.59 Reducing the PM2.5 level to recommended
standards was estimated to potentially decrease the
prevalence of hypertension by 15%.59
Figure 2. Trends in age-standardized summary exposure value of high systolic blood pressure, for the World Bank regions from
1990 to 2019.
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729 April 2, 2021 813
Schutte et al Hypertension in LMICs
With the rapid migration of vast populations from rural
to urban areas in most LMICs, it is now clear that the con-
fluence of several exposures accompanying urbanization
is conducive to the rapid development of hypertension.
Urbanization leads to a nutrition transition (consumption
of foods high in fat, salt, and sugar and low in fruits and
vegetables), a decrease in physical activity, adoption of
a sedentary lifestyle, greater access to tobacco, alcohol,
and other unhealthy substances, and exposure to an
environment characterized by pollution (air, water, light,
and noise), stress, and a lower amount of green spaces.
Understanding these pathways is essential to develop
and implement interventions to prevent and curb hyper-
tension development in this rapidly growing population.
Developmental Origins of Health and
Exposures Across the Life Course
Epidemiological studies have examined the association
between low birth weight and adult BP.60–62 The global
prevalence of low birth weight in 2015 was estimated
to be 14.6% (95% CI, 12.4–17.1). But the prevalence
in southern Asia was much higher at 26.4% (95% CI,
18.6–35.2). The prevalence in Sub-Saharan Africa was
slightly lower than the global estimate at 14.0% (95%
CI, 12.2–17.2). Southeast Asia and Oceania (excluding
Australia and New Zealand) and northern Africa too had
lower prevalence at 12.2%.63
Low birth weight affects kidney structure and func-
tion, is associated with an increase in large artery stiff-
ness,64 a reduction in the size of the aorta,65 and an
increase in aortic wall thickness, which may result in
early vascular aging66 (Figure 4). There is a cyclical
relationship between hypertension and endothelial
dysfunction—worsening of one may lead to worsening
of the other.68
The mechanisms by which low birth weight affects BP
are complex and involve nutrition, inflammation, gluco-
corticoids, and epigenetic changes.69–73 It is, therefore, of
paramount importance to improve nutritional quality dur-
ing the first 1000 days of life, spanning from pregnancy
to approximately age two (Figure 4), as it has far-reaching
effects for future cardiovascular and metabolic health,
cognition, and sociobehavioral development. These
putative lifecourse risk factors, including low socioeco-
nomic status, poor growth, shorter leg length, poor diet,
and obesity, are strongly associated with chronic dis-
eases in adult life and of increasing relevance in LMICs.74
PREVENTION AND MANAGEMENT:
IMPLEMENTATION BARRIERS AND
ACTIONS
Awareness, Treatment, and Control
Global hypertension disparities are substantial and con-
tinue to increase.75 When comparing HICs with LMICs
from 2000 to 2010, the proportions of awareness,
treatment, and control improved by ≥10% in HICs. In
LMICs, however, improvements were limited for aware-
ness (32.3%–37.9%) and treatment (24.9%–29.0%)
and even slightly declined for control (8.4%–7.7%).75 A
recent analysis of individual-level data from 1.1 million
adults in nationally representative samples in 44 LMICs
reports that among those with hypertension, 26% had
never had their BP measured, 39% had been diag-
nosed with hypertension before the survey, 30% had
been treated, and only 10% had achieved control of their
hypertension.15 The best hypertension care performance
was found in Latin America and the Caribbean, whereas
countries in Sub-Saharan Africa tended to show the
poorest performance.
The first significant barrier to address in LMICs is
its exceptionally poor awareness. The Lancet Commis-
sion on Hypertension proposed that “every adult should
know their BP”—a critically important starting point.67
In response to this call, the ISH launched a global BP
measurement awareness campaign, namely May Mea-
surement Month, screening >4.2 million adults from
2017 to 2019.10 In 2019, 92 countries participated,
and of the 1.5 million screenees, one-third had never
had a BP measurement taken before.9 It is difficult to
comprehend that a BP measurement, which is arguably
the cheapest, easiest, and the most essential first step
and convenient method to assess cardiovascular risk, is
still not widely implemented.
With hypertension control rates of ≈10% in LMICs,15
and with significant population boom occurring among
many LMICs, there is a need for radical improvement
in detection and treatment strategies. However, the
implementation of hypertension control strategies in
low-resource settings depends largely on cost consid-
erations.76 A recent review of economic evaluations of
hypertension treatment programmes across 15 LMICs
found hypertension control to be a highly cost-effective
intervention. However, there are apparent gaps in evi-
dence on critical programme elements to improve cost-
effectiveness. These include task-sharing strategies and
standardized treatment protocols.76
Table 2. Healthy Lifestyle and SBP
Modification SBP reduction, mm Hg
Weight reduction 5–20 mm Hg per 10 kg
of weight loss27,28
Adopting DASH diet 8–1429,30
Dietary salt/sodium reduction 2–829–31
Physical activity 4–932,33
Moderation in alcohol consumption 2–434
DASH indicates Dietary Approaches to Stop Hypertension; and SBP, systolic
blood pressure.
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
814 April 2, 2021 Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729
Schutte et al Hypertension in LMICs
Population-Based Approaches to Improve
Cardiovascular Health
For improved control of hypertension, the individualized,
targeted approach requires interventions to increase
awareness, treatment, and control.77,78 Individualized
approaches are reliant on sufficient capacity by the health
care system to ensure effective delivery of care—an
aspect that remains challenging in LMICs as reflected by
low physician-to-patient ratios and access to medicines.
The emphasis is on curative care, rather than prevention.
Corresponding preventive population-based
approaches involve interventions designed to achieve a
small reduction in BP in the entire population. This mass
approach, initially proposed by Geoffrey Rose,79 has the
potential to be far more effective by lowering the broader
population risk in both hypertensives and normotensives.
The scope of population-based approaches that
would be most effective in LMICs remains an impor-
tant area of research. An overall understanding is that
health-promoting environments should be created that
encourage healthier living across the lifecourse, from
preconception to the elderly67 (Figure 4). This is highly
relevant to LMICs where hypertension often occurs
at younger ages (early vascular aging), and there is a
growing burden of those with prehypertension, whose
conversion to hypertension can be prevented or delayed
through population-wide measures.
Such population-based approaches involve broad
brush strokes and include the implementation of policies
that support using sin taxes for, for example, tobacco,
alcohol, and sugar-sweetened beverages, smoking
restrictions, and ensuring safe built environments with
sufficient green space that promotes mental health and
physical activity. Ideally, sin tax revenue should be used
to subsidize healthier food choices such as fruits and
vegetables, which not only address the emerging obe-
sity epidemic but would importantly increase potassium
intake and other essential micronutrients.67 A modeling
study suggests that sugar tax would produce the big-
gest gains in health, followed by salt tax, saturated fat
tax, and sugar-sweetened beverage tax.80 Salt-reduction
initiatives (such as industry engagement to reformulate
products and the establishment of sodium content tar-
gets for foods) have been implemented widely, with 75
countries having a national salt-reduction strategy in
2015; yet, the authors conclude that wider initiation of
strategies particularly in LMICs will be vital to achieving
the WHO Member States target of a 30% global reduc-
tion in salt intake by 2025.81 Other policy approaches
should also gain higher priority on the agenda of health
authorities in LMICs, such as best buys to impact future
lifestyles including marketing (banning alcohol and fast
food advertising).82 Front-of-packet food labels were
shown to encourage healthier choices made, and poten-
tially a traffic light system may be implemented in regions
with limited literacy levels.83
Hypertension Guidelines Targeting LMICs
In response to the startling reality that over three-quar-
ters of heart disease and stroke-related deaths occur in
Figure 3. Relationship between poverty and noncommunicable diseases.
Reprinted from World Health Organization46 with permission. Copyright © 2010, WHO.
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729 April 2, 2021 815
Schutte et al Hypertension in LMICs
LMICs, the WHO and the US Centres for Disease Con-
trol and Prevention launched the Global Hearts Initiative.
In partnership with several global organizations such as
the American Heart Association, ISH, and Resolve to
Save Lives, the HEARTS technical package84 was devel-
oped with modules spanning
• Healthy-lifestyle counseling,
• Evidence-based treatment protocols,
• Access to essential medicines and technology,
• Risk-based CVD management,
• Team-based care, and
• Systems for monitoring.
This package is intended for use by policy makers
and program managers within Ministries of Health and
resource-limited settings. With availability in several lan-
guages, the implementation of the package should be
promoted widely.
In recognition of the apparent shift of the highest
BPs from high-income to low-income regions,85 the ISH
released the 2020 ISH Global Hypertension Practice
Guidelines25 and specifically tailored essential and opti-
mal standards of care for the management of hyperten-
sion in low- and high-resource settings. While excellent
evidence-based and thorough guidelines were released
in the United States1 and Europe86 in previous years,
these guidelines were designed for optimal care in HICs,
and are thus not fit for a global purpose. The 2020 ISH
Guidelines were produced in a practical format that is
easy to use and to adapt according to local settings into
national guidelines. It is relevant to low- but also high-
resource settings for use by clinicians, nurses, and com-
munity health workers, as appropriate.
Aspects Relevant to LMICs Regarding
Measurement and Diagnosis
Despite BP measurement being one of the most impor-
tant tests in clinical medicine, inaccurate measurements
can lead to diagnostic and management errors, and there
remain major challenges in LMICs, particularly relating to
the following:
Use of BP Devices That Are Not Validated for
Accuracy
Since most BP devices available on the market are
not validated for accuracy and generally cheaper than
validated ones, health care officials in LMICs often pur-
chase inappropriate devices.87 Appropriate devices are
listed on the STRIDE BP website (www.stridebp.org). In
response to concerns about the lack of accurate, good-
quality devices in LMICs, the WHO in 2020 published an
updated report on technical specifications for automated
Figure 4. Early-life effects and preventive efforts across the life course to manage raised blood pressure (BP).
CV indicates cardiovascular; and QOL, quality of life. Reprinted from Olsen et al67 with permission. Copyright © 2016, Elsevier, Lancet.
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
816 April 2, 2021 Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729
Schutte et al Hypertension in LMICs
noninvasive BP-measuring devices with a cuff.88 The
WHO recognizes that automated measurements are
gradually replacing manual BP measurement due to
environmental concerns about mercury, poor calibration,
and improper measurement with auscultatory devices,
while acknowledging the superior, consistent accuracy
of validated automated devices.88
Availability of BP Devices in Low-Resource
Settings, Including Rural and Urban Health Care
Environments
Key stakeholders expressed their concerns around the
lack of accurate, good-quality BP devices, especially in
LMICs, at a workshop on BP measurement during the
Fourth WHO Global Forum on Medical Devices hosted
by the Government of India in 2018.89 The 2020 WHO
technical report88 on specifications of devices was devel-
oped in response to this concern, and although the
report would assist implementers in procuring validated
devices, the availability of devices in rural and urban set-
tings cannot be guaranteed unless governments make
active engagement. This is undoubtedly feasible when
there is a political will, as was demonstrated by the
HEARTS in the Americas program of the Pan American
Health Organization, which held a meeting shortly fol-
lowing the release of the WHO Report to examine how
national governments could best implement the recom-
mendations. It is reassuring that several national govern-
ment agencies were in the position to respond swiftly
in introducing aligned device procurement policies. Cuba
had already adopted many of the recommendations of
the WHO report, including a certification course for BP
measurement and the production, testing, and use of
accuracy-validated electronic BP devices.
Optimizing the Performance of Health Care
Practitioners in BP Measurement—Whether
Clinicians, Nurses, or Community Health Workers
Accurate BP measurement is critical, even when using
an automated validated device as recommended. A
5-mm Hg measurement error may lead to incorrect
hypertension status classification in 84 million individu-
als worldwide.90 A high-level recognition by government
agencies is required on the importance and scope of
proper hypertension care, which includes several practi-
cal aspects. Implementing team-based care, using a ded-
icated measurement workstation, and ensuring observer
training (and retraining) is critical, especially since no-cost
certification programmes are available for resource-con-
straint settings (eg, https://globalhypertensionathopkins.
org/courses and www.stridebp.org/training).90
Most challenges in BP measurement faced by LMICs
are relevant to the office or clinic BP measurement. But
it should now be acknowledged that office BP mea-
surement poses several challenges in the management
of hypertension due to the variable nature of BP, which
is why several hypertension guidelines propose that
out-of-office measurements, especially 24-hour ambula-
tory BP, be used to diagnose hypertension.1,25,86 In rec-
ognition of the challenges of financial resources and
workforce capacity to implement ambulatory BP mea-
surements in LMICs, the 2020 ISH Guidelines recom-
mended that home and ambulatory BP measurements
be implemented, where available and possible. The
potential for wider implementation of home BP measure-
ment in LMICs is excellent and has been proven fea-
sible in Nigeria,91 Argentina,92 Mexico, and Honduras.93
In Table 3, a summary on the usefulness of office and
out-of-office measurement methods is provided, about
resource-constraint settings.
Challenges in Modifying Lifestyle and Health
Behaviors in LMICs
The appetite of health care providers and patients to
actively engage and change unhealthy behaviors is low,
often achieving poor results.94 This is even more chal-
lenging in LMICs where rural and urban clinics are faced
with high volumes of patients and limited numbers of
health care staff to discuss these options carefully.
Challenges include: several complex societal factors
are unique in LMICs that would prohibit people from fol-
lowing a healthy lifestyle and require acknowledgment
and understanding by policymakers to successfully
implement interventions. LMICs are often challenged by
a double burden of malnutrition,39 and these changing
dynamics in nutrition have directly affected the poor-
est LMICs with increases in obesity mainly due to rapid
changes in the food system. The dominant contributors
include the availability and uptake of cheap ultra-pro-
cessed food and beverages and activity-saving technolo-
gies resulting in major reductions in physical activity at
work and in leisure times.39 Several environmental fac-
tors may also discourage people from becoming more
active, such as low air quality and pollution, high-density
traffic, fear of crime and violence in outdoor areas, and
limited green space, parks, sidewalks, and recreation
facilities for activities.95
As with population-based interventions to improve
lifestyle across the lifecourse, global population-based,
multisectoral, multidisciplinary, and culturally relevant pol-
icies need to be implemented to create health-promoting
environments.67
Pharmacotherapy in LMICs
The pharmacological treatment of hypertension is
arguably the most evidence-based and cost-effec-
tive medical intervention ever, with clear benefits of
reduced morbidity and mortality while saving costs as
evident from many clinical trials.96 Besides, BP medi-
cations are cheap, even in LMICs. A recent review on
drug costs in LMICs reports a median monthly cost
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729 April 2, 2021 817
Schutte et al Hypertension in LMICs
of US $11 for ACE (angiotensin-converting enzyme)
inhibitors, $17 for angiotensin-II receptor blockers,
$6.56 for calcium-channel blockers, and $1.77 for
diuretics.76
Yet, only about 10% of patients with hypertension in
LMICs are controlled.15 It is, therefore, imperative to iden-
tify and address the roadblocks as to why hypertension is
not treated appropriately.
Availability and Overall Affordability
The PURE study (Prospective Urban Rural Epidemiol-
ogy) recently assessed the availability and affordability
of antihypertensive medicines in 158 274 individuals
from 20 countries.97 They found a lower availability of ≥2
drug classes in LMICs compared with HICs. Only 13% of
communities in LIC (9 of 68 communities) had access to
all 4 drug classes. Availability of antihypertensive medi-
cations has a profound effect on overall BP control, as it
was shown that participants with known hypertension in
communities with access to all 4 drug classes were more
likely to use at least 1 medicine (odds ratio [OR], 2.23;
P<0.001), combination therapy (OR, 1.53; P=0.054),
and to have their BP controlled (OR, 2.06; P<0.001).97
But apart from availability, affordability is also critical in
resource-constrained settings. In PURE, it was reported
that participants with hypertension from more affluent
households were able to afford the 4 drug classes, were
more likely to use at least 1 medicine, combination ther-
apy, and to have their BP controlled, than those unable to
afford the medicines.97
Monotherapy Versus SPC Therapy
Fixed-dose combination, also referred to as SPC ther-
apies, is increasingly recommended for initial or early
management of patients with hypertension.25,86 The
WHO also included dual combination therapy for hyper-
tension in their 2019 Essential Medicines List98 thereby
encouraging individual countries to do the same. Most
patients with hypertension generally require BP-lower-
ing medication from multiple classes to achieve control.
Accumulating evidence indicates that SPCs have sig-
nificant benefits beyond monotherapy to contribute to
attaining BP control, including (1) reducing treatment
complexity, (2) accelerating the time taken to achieve
control, (3) improving patient adherence, (4) fewer side
effects, and (5) reducing therapeutic inertia.86,99
SPC therapy seems a feasible solution for LMICs in
terms of effectiveness, safety, and cost-effectiveness.
Effectiveness in lowering BP was demonstrated using
a novel low-dose triple SPC in Sri Lanka. In the TRI-
UMPH trial (Triple Pill Versus Usual Care Management
for Patients With Mild-to-Moderate Hypertension), low-
dose triple SPCs achieved 70% BP control in a single
treatment step, without increased withdrawals due to
adverse effects, which was superior to usual care.100 In
terms of the cost of dual SPCs, they seem at present
comparatively expensive in some LMICs, for example, US
$0.10 to 0.33 per day in Nigeria and Kenya. However, in
Uganda, SPCs including amlodipine, losartan, and hydro-
chlorothiazide were procured from the Novartis Access
programme for US $0.03 per pill. With more coherent
collaborative efforts, similar approaches can be imple-
mented on a much wider scale in LMICs.
Wider implementation of polypills that include not
only antihypertensive agents but also statins may also
become a highly effective approach in LMICs. The recent
TIPS-3 randomized trial (The International Polycap Study
3) found that a polypill (containing simvastatin, atenolol,
hydrochlorothiazide, and ramipril) plus aspirin led to a
lower incidence of cardiovascular events than placebo in
participants without CVD.101
Clinical or Therapeutic Inertia
Treatment inertia “happens when a clinician does not
initiate or intensify therapy in a patient who has not
achieved therapeutic goals.”102 A recent real-world
study of 100 982 hypertensive patients initiated on
monotherapy showed that treatment intensification
occurred in only 22% of patients after 6 months and
Table 3. Usefulness of Office and Out-of-Office BP Measurement Methods in Low-Resource Settings
Best for
Office BP
Out-of-office BP
24-h ambulatory BP Home BP
Routine screening of
untreated individuals. To
follow-up treated patients*
Preferred method for di-
agnosis of hypertension if
available*
Preferred method for long-
term follow-up of patients
using treatment
Screening +++ − +
Initial diagnosis ++* +++ ++
Medication dose adjustment + +++ ++
Follow-up ++ + +++
Affordability +++ + +++
Hypertension diagnosis, mm Hg ≥140/90 ≥130/80 ≥135/85
BP indicates blood pressure.
*Office or clinic BP could be used to diagnose hypertension, but if possible, it should not be made on a single office visit (usually 2–3
visits in 1–4 wk).25 If possible and available, ambulatory BP should be used for diagnosis of hypertension – albeit usually unrealistic in
low-resource settings.
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
818 April 2, 2021 Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729
Schutte et al Hypertension in LMICs
36% of patients after 3 years.103 The impact appears
even greater in LMICs, where studies in Nigeria,
Ghana, and South Africa found that treatment was not
increased in up to 90% of patients with uncontrolled
BP. 104 Strategies to address inertia include the use of
SPCs and simplified treatment protocols that can be
followed by community health workers, nurses, and
clinicians, which includes specific steps for treatment
intensification.
Treatment Adherence
“Medicines do not work if you do not take them.” This
sentence summarizes the issue of medication adher-
ence—an important determinant of treatment success.
Nonadherence to medication for hypertension results in
uncontrolled BP, leading to cardiovascular complications.
Apart from poor health outcomes, nonadherence leads
to increased health care costs, which the health systems
of LMICs cannot afford.105 Epidemiological studies use
different scales to measure adherence. The Morisky
Medication Adherence Scale and its modified version,106
the Hill-Bone Compliance scale,107 and the Medication
adherence inventory and inventory of adherence to self-
management108 are some examples of adherence mea-
surement scales.
A systematic review and meta-analysis published
in 2017 looked at nonadherence to antihypertensive
medication in LMICs.109 The nonadherence ranged
from 14.5% to 93.3%. The overall percentage of non-
adherence, when measured using the Morisky Medi-
cation Adherence Scale (8-item), was 63% (95%
CI, 39–88), whereas that using 80% and 90% cut-
off scales was 25% (95% CI, 17–34). Older age
(adjusted OR [aOR], 0.98 [95% CI, 0.96–0.99]), being
female (aOR, 0.72 [95% CI, 0.53–1.00]), and having
controlled BP (aOR, 0.58 [95% CI, 0.36–0.96]) lowers
the odds of being nonadherent.110 Data from low- and
middle-income Sub-Saharan African countries show
that percentage of low, medium, and high adherence
was 30.8%, 33.6%, and 35.6%, respectively. Factors
associated with a low adherence were the use of tra-
ditional medicines (aOR, 2.28 [95% CI, 1.79–2.90])
and low and middle individual wealth (aOR, 1.86 [95%
CI, 1.35–2.56]) compared with high individual wealth.
The main reasons reported for not taking the medi-
cines were forgetfulness (34.3%), high cost of treat-
ment (26.0%), side effects (16.8%), and feeling well
(11.8%).111 It has been shown that nonadherence is
usually <10% with SPCs, rising to ≈20% with 2 pills,
≈40% with 3 pills, and high rates of partial or com-
plete nonadherence in patients receiving ≥5 pills.86
Multicomponent intervention targeted at patients (eg,
reminders), physicians (eg, improved communication
skills), drug treatment (eg, reducing pill burden), and
health systems (eg, accessibility and affordability) may
help to reduce nonadherence to treatment.112
COVID-19–RELATED CHALLENGES IN
MANAGING HYPERTENSION IN LMICS
Notwithstanding the status that hypertension is the lead-
ing risk factor for death in the world,113 it continues to
compete with other major health threats in LMICs, such
as HIV, tuberculosis, malaria, and malnutrition. More
recently, the coronavirus disease 2019 (COVID-19) had
an acute global impact on health systems, with LMICs
being no exception. This inevitably continues to affect
hypertension management.
Globally, the aggressive COVID-related lockdown
and social isolation strategies had a profound effect
on patients. Not only had it an impact on their mental
health, but those with known CVD, including hyperten-
sion, generally avoided going to health care facilities. This
was evident from a substantial drop in hospital admis-
sions for stroke and myocardial infarction in HICs.109
In Europe, Hypertension Excellence Centres reported
shutting down for an average of 9 weeks, resulting in
the number of patients treated per week decreasing by
90%.114 In LMICs, patient barriers stretch beyond those
in HICs, and with the pandemic having a more severe
impact on unemployment, financial stresses resulting in
not filling medication prescriptions that in turn may result
in increased risk for complications and telehealth may
limit access to less tech-savvy patients. On the health
system level, barriers include diversification of finances
to fund the COVID-19 response, disruption of medical
supply chains, canceling of clinics during lockdowns, and
social distancing limiting access to care.115
Importantly, patients with hypertension face a sig-
nificantly greater risk for adverse COVID-19–related
outcomes, independent of age, and require careful
hypertension management.
Misinformation on the use of ACE inhibitors or angio-
tensin-II receptor blockers also resulted in confusion
among millions of patients and clinicians.109,114 Rapid
responses by global hypertension societies ensured that
messaging is reinforced, recommending that ACE inhibi-
tor/angiotensin-II receptor blocker therapy should not be
stopped or changed, which was later confirmed by obser-
vational studies and clinical trials.
With compromises in hypertension care during emer-
gencies such as COVID-19, it becomes evident that new
strategies for hypertension care are required, such as
virtual clinics, telemedicine, as well as mHealth (mobile
health) and eHealth (electronic technologies in health)
strategies,109,114 including home BP monitoring. While
these solutions may hold value in HIC, its potential for
sustainable improvements in hypertension care in LMICs
may be much greater, mainly due to limited health care
workforce capacity.
In the longer term, LMICs may face more severe con-
sequences than HICs. The pandemic not only affected
morbidity and mortality but is already resulting in massive
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729 April 2, 2021 819
Schutte et al Hypertension in LMICs
economic and physical hardships increasing health
inequalities.115 Social isolation is impossible in single-
room households with >6 family members109 or when
sharing taxis in public transport. With stay-at-home strat-
egies implemented, a no-work no-pay approach has a
direct impact on household income. A sudden loss in
income, or access to social support, socioeconomic vul-
nerabilities are significantly enhanced. With the acute
challenges of COVID-19, hypertension management
receives even less attention despite warnings that the
hypertension crisis should not be separated from overall
health care strategies.115
There is now unprecedented global demand for a
COVID-19 vaccine. Claims are made to support vaccine
allocation also to LMICs, and tough decisions are faced
by policymakers who should ensure that vaccines are
first given to those who need them most.
HEALTH SYSTEM CHALLENGES
Physician-to-Patient Ratio and Nurse-to-Patient
Ratio
Achieving universal health coverage (UHC) is dependent
on the availability, accessibility, and acceptability of high-
quality health workforce. For the year 2018, India, Nigeria,
and Mozambique, all LMICs, reported 0.9, 0.4, and 0.1 phy-
sicians per 1000 people, respectively. This is in contrast to
Japan, an HIC, which reported 2.4 physicians per 1000
people in 2016.116 Similarly, India, Nigeria, and Mozam-
bique reported 1.7, 1.2, and 0.7 nurses and midwives per
1000 people in 2018, respectively, far lower than 12.2 for
Japan in the same year.117 The WHO estimates a shortfall
of 18 million health workforce staff by 2030, mostly in the
LMICs.118 The shortage is due to many factors—underin-
vestment in education and training, mismatch in education
and employment, the problem in posting of the workforce
to rural and remote areas where the shortfall is pronounced,
low remuneration, and migration of workforce from LMICs
to HICs for better employment opportunities.118 To over-
come the shortfall, governments are required to address
issues resulting in health labor market failures, maximize
women’s participation in the health sector, prioritize invest-
ment in education, organize health systems toward preven-
tion and primary care and away from clinical specialties and
hospitals, and secure health financing to invest in health
workforce to ensure right skill mix and working condition.119
Unmet Need for Hypertension Care in LMICs
When reviewing the care cascade in LMICs by the pro-
portions of patients with hypertension, namely those
(1) unscreened and undiagnosed, (2) diagnosed but
untreated, (3) treated but uncontrolled, and (4) treated
and controlled, it is apparent that there is a signifi-
cant unmet need in hypertension care. For instance, in
Sub-Saharan Africa, these figures reflect 73% being
unaware and untreated, 18% were treated, but only 7%
were treated and controlled.120
For this reason, there is a global movement toward
UHC aligned with the Sustainable Developmental Goal
3.8 target, which aims to achieve UHC. A recent analy-
sis of the GBD data showed that global UHC effective
coverage index improved from 45.8 (95% uncertainty
index, 44.2–47.5) in 1990 to 60.3 (95% uncertainty
index, 58.7–61.9) in 2019. When compared with HICs
in 2018 (85.8), countries in Southeast Asia, East Asia
and Oceania (64.2), South Asia (46.0), and Sub-Saharan
Africa (43.9) had lower UHC coverage index.121 Achiev-
ing UHC requires health system strengthening including
increased numbers of well-trained health care staff and
efficient procurement and medication access—aspects
crucial to improve hypertension care. Achieving UHC can
thus improve hypertension treatment and control rates
as health system strengthening is central to achieving.122
High Out-of-Pocket Payments
Out-of-pocket payments are those payments made by
individuals to health care providers at the time-of-service
use. When these payments are large relative to a family’s
total income, it is termed as catastrophic out-of-pocket
spending. In 2010, an estimated 808 million people world-
wide incurred catastrophic health spending. The propor-
tion of population incurring catastrophic health spending
in Africa, Asia and Latin America, and the Caribbean was
11.4%, 12.8%, and 14.8%, respectively, compared with
the global proportion of 11.7%.123 Poor, less educated,
rural, female-headed households, and households with
members with chronic conditions are more likely to incur
catastrophic health expenditure.124,125 Households with
a member diagnosed with hypertension experiencing
catastrophic health expenditure and impoverished due
to health expenditure were high in LMICs compared with
households with no member diagnosed with hypertension
or NCD.126 Direct medical expenses toward consultation,
laboratory tests, medication, hospitalization, and emer-
gency care and indirect expenses toward transportation,
food, and nonpharmacological treatment constituted a
patient’s annual out-of-pocket expenditure for hyperten-
sion care.127 Strategies to reduce these payments are
(1) abolish user fees and charges in public facilities, (2)
exempt specific population subgroups from paying for
health services, and (3) exempt specific health services
from payment. These strategies need political support,
decision-making, and proper preparation.128
Leveraging Technology for Hypertension
Management (mHealth and eHealth)
The Global Observatory of eHealth defines mHealth or
mobile Health as “medical and public health practice
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
820 April 2, 2021 Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729
Schutte et al Hypertension in LMICs
supported by mobile devices such as smartphones,
patient monitoring devices, personal digital assistants
and other wireless devices.”129 Mobile phones are the
primary means of internet access in LMICs. Of the total
3.5 billion people connected to mobile internet, 2.6 bil-
lion live in LMICs representing just over 40% of the total
LMIC population.130 mHealth is a powerful tool that can
provide health education, promote behavior change, aid
diagnosis through the use of a decision support system,
and ensure record linkages. Many projects with the aim
to improve detection and management of hypertension in
select LMICs have used mHealth technology to identify,
track, and follow-up patients with hypertension; improve
medication adherence; and educate patients and com-
munity health workers.131,132
A systematic review published in 2020 reported that
mHealth interventions reduced SBP by 2.99 mm Hg
(weighted mean difference [WMD] [95% CI, 1.80–
4.19]). But when the effect on SBP was restricted to
studies conducted in developing countries, the reduc-
tion was not statistically significant (0.25 mm Hg, WMD
[95% CI, −3.10 to 3.59]). The interventions included in
the review were text messages, calls, mobile phone appli-
cations, and wearable or portable monitoring devices.133
The evidence on clinical decision support systems
from a cluster randomized controlled trial done in pub-
lic health facilities in India shows that SBP reduced by
0.31 mm Hg (95% CI, −3.91 to 3.29) in the intervention
arm compared with the enhanced usual care arm.134 But
when decision support system was compared with the
chart-based system, the SBP reduced by 6.59 mm Hg
(95% CI, −12.18 to −1.42).135 A cluster randomized trial
conducted in India and Tibet to test the effectiveness
of a lifestyle modification plus appropriate medication
intervention delivered by community health workers
aided by an electronic decision support system led to a
reduction of SBP by 2.7 mm Hg (P=0.04).136 Adoption
of mHealth to improve health system performance may
lead to improving the quality of health care and closing
the gap to attain UHC.
Team-Based Care (Task Sharing)
The WHO describes task sharing as “rational redis-
tribution of tasks among health workforce team”
wherein “specific tasks are moved, where appropriate,
from highly qualified health workers (eg, physicians)
to health workers (eg, community health workers)
with fewer qualifications after adequate training.”137
The concept of task sharing arose due to the lack of
personnel in the health systems of many countries in
Africa affected by the HIV pandemic. It was a strat-
egy to address the low capacity of existing health per-
sonnel and add a new cadre of workers to the health
system.138 In LMICs, task sharing has been shown to
improve outcomes in various domains—maternal and
child health, immunization, HIV/AIDS, malaria, and
tuberculosis.139–142 A systematic review reported that
task sharing is cost-effective for a range of conditions
in LMIC settings.143 Even for NCDs, evidence exists on
the effectiveness of task sharing.144
A study conducted in 4 LMICs (Bangladesh, Gua-
temala, Mexico, and South Africa) reported that com-
munity health workers could successfully screen people
for NCD risk factors including high SBP after exten-
sive training.145 The mean level of agreement between
risk scores assigned by the health workers and that by
the health professionals was 96.8% (weighted κ, 0.948
[95% CI, 0.936–0.961]) with little between-country
variation.
A systematic review and meta-analysis of 63 studies
on task sharing with nonphysician health workers for
BP management in LMICs found that SBP reduced by
4.85 mm Hg (95% CI, 3.57–6.12), whereas diastolic BP
reduced by 2.92 mm Hg (95% CI, 2.09–3.75).146 The
reduction in BP differed by categories of nonphysician
health workers—highest for pharmacists and lowest for
community health workers (8.12 vs 3.67 mm Hg). The
components of the intervention in the included studies
were education about lifestyle modification, home vis-
its, algorithm-based management of hypertension, and
referral system. The enablers to task sharing are train-
ing of nonphysician health workers, provision of sim-
ple and clear algorithms, protocols and guidelines for
screening, treatment and titration of drug dosage, and
availability of drugs in health facilities. The barriers were
staff retention, irregular drug supplies, and nonavail-
ability of sphygmomanometers.144 A carefully designed
task-sharing program embedded within the health sys-
tems can address the factors mentioned above.
RESEARCH GAPS AND
RECOMMENDATIONS
In this section, we provide some solutions to achieve
BP control and recommendations for further research.
Table 4 lists some barriers to achieve BP reduction at the
patient, provider, and health system level together with
the solutions.
Appropriate research in LMICs can help bridge sev-
eral gaps in the current evidence for the management
of hypertension for which contextual attention is needed.
Some of these are summarized below:
1. Conduct clinical trials on improving BP control in
LMICs in specific contexts, such as Sub-Saharan
Africa, South Asia, and East Asia, focusing on
effectiveness, cost-effectiveness, and safety of
tailor-made local interventions. An example is the
CREOLE trial,147 which looked at 2-drug combi-
nation therapy for control of hypertension among
Black African patients with hypertension. Another
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729 April 2, 2021 821
Schutte et al Hypertension in LMICs
relevant example is the TRIUMPH study, conducted
in Sri Lanka, which increased proportion of patients
achieving their target BP goal versus usual care.100
2. Undertake context-specific studies to effectively
implement proven evidence-based strategies
(including mHealth) to bridge the know-do gap
for rolling out promotive, preventive, and therapeu-
tic interventions in LMIC settings, especially for
rural, remote, poor, and disadvantaged populations.
Recent studies from India indicate that task shar-
ing and contextualized collaborative care models
utilizing nonphysician health workers enabled with
mHealth can improve hypertension and diabetes
detection and control.148,149
3. Determine the effectiveness of different screen-
ing strategies (mass, targeted, or opportunistic) on
advancing early detection and treatment initiation for
hypertension.
4. Conduct research on effective implementation
strategies for promoting healthy diets such as fruit
and vegetable intake, reducing salt intake, regulat-
ing the sale of alcohol, and improving the environ-
ment by reducing air and other sources of pollution.
5. Undertake systematic reviews on determining the cost-
effectiveness of interventions to reduce BP, contextual-
ized to the unique health system settings of LMICs.
6. Build the evidence base on emerging risk factors
for hypertension such as air and noise pollution,
Table 4. Barriers to BP Reduction at the Patient, Provider, and Health System Levels and Potential Solu-
tions to These Barriers
Level Barriers Solutions
Patient Inadequate access to hypertension
care
Task sharing
Virtual consultations with physicians via telemedicine (after the first visit,
confirmation of diagnosis) for regular follow-up
Poor awareness of hypertension Leverage technology to disseminate information on hypertension
Community-level activities to generate awareness
Community-level events for hypertension screening (eg, May Measure-
ment Month)
Low treatment adherence due to as-
ymptomatic nature of hypertension
Counseling by physicians/nurses at the health facility and by frontline
health workers in the community to encourage patients to take medica-
tion regularly
mHealth technology, in the form of apps, to remind patients to take
medication regularly and monitor adherence
Ensuring availability and affordability of quality medicines
Socioeconomic issues UHC
Insurance schemes to cover costs associated with outpatient visits,
medication, and laboratory tests
Provider
Lack of knowledge about the con-
cept of absolute risk
Training through virtual learning courses such as “Implementation of the
HEARTS Technical Package in Primary Health Care” by the Pan Ameri-
can Health Organization (https://www.campusvirtualsp.org/en/course/
virtual-course-implementation-hearts-technical-package-primary-health-
care) and “Fundamentals for Implementing a Hypertension Program in
Resource-Constrained Settings” by Global Hypertension at Hopkins
(https://globalhypertensionathopkins.org/courses)
Time constraints in estimating abso-
lute risk
mHealth technology
Feeling of lack of autonomy and dif-
fidence among lower level health
care staff
Capacity building programs with a mix of face-to-face and distant learn-
ing for clinicians and health workers
Health system Lack of trained health care staff in
hypertension management
Training for clinicians. For example, the Certificate Course in Manage-
ment of Hypertension in India aims to train clinicians to manage hyper-
tension using the latest available evidence. The course is designed by
national and international experts together with participation of the ISH
and British and Irish Hypertension Society
Drug procurement, availability, distri-
bution, and frequent stockouts
Development of a list of core medicines based on recent evidence on
the efficacy, safety, and cost
Robust IT system to streamline drug procurement and distribution
Poor surveillance and screening
practices
Set up simplified surveillance system to monitor BP trends in the popula-
tion and also among patients
Community-level screening for hypertension through frontline health
workers and opportunistic screening at the health facilities
app indicates application; BP, blood pressure; ISH, International Society of Hypertension; IT, information technology; mHealth, mobile
health; and UHC, universal health coverage.
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
822 April 2, 2021 Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729
Schutte et al Hypertension in LMICs
light (as a proxy for urbanization), green space and
the built environment, and neighborhood walkabil-
ity. Data from cohort studies in combination with
environmental data from secondary sources (eg,
PM2.5 levels, satellite imagery to assess change in
green cover) would be required.
7. Conduct research on effectively involving commu-
nity self-help groups to promote awareness regard-
ing hypertension and to implement BP-reduction
strategies. The feasibility of implementing fam-
ily- and community-based interventions to reduce
risk factors for hypertension, which usually tends
to cluster at household level,150,151 should also be
explored.
8. Evaluate newer interventions like renal denerva-
tion, baroreflex activation therapy, and carotid body
ablation and their appropriateness for treating
hypertension in LMICs.
Potential funding sources available to conduct
research on hypertension in LMICs include but are
not limited to (1) the Global Alliance for Chronic Dis-
ease, “an alliance of research funders jointly funding
research into chronic disease” including hyperten-
sion,152 (2) the Fogarty International Centre of National
Institutes of Health,153 (3) the Wellcome Trust154 and
National Institute for Health Research,155 and (4) the
National Health and Medical Research Council of
Australia.156 Apart from global opportunities, country-
specific opportunities are also available such as the
Wellcome Trust–Department of Biotechnology India
Alliance partnership157 and the South African Medical
Research Council.158 Governmental and nongovern-
mental organizations can apply to LINKS159 for 1-time
grants for research to improve cardiovascular health,
including hypertension control. The Global Environ-
mental and Occupational Health funded by the Fog-
arty International Centre has currently 7 hubs based in
various LMICs conducting research on environmental
risk factors.160 Some are investigating the relationship
between air pollution, arsenic, and hypertension. The
Kathmandu Declaration161 recognizes various gaps
that hinder prevention and control of hypertension
and CVD in LMICs and provides recommendations to
advance implementation research.
As a final recommendation, the WHO report titled
“Scaling Up Action Against Noncommunicable Dis-
eases: How Much Will It Cost?”162 provides a helpful
matrix for population-based NCD prevention mea-
sures, which can be adapted for hypertension control,
including relevant steps to introduce sodium reduction
for hypertension control (preparation of an evidence
base and baseline assessments [year 1], draft leg-
islation and consultation [eg, front of package label-
ing], inviting comments from experts and public [year
2], legislation and information campaign [year 3], and
periodic national-level surveys to measure the impact
[continuous]). There are clear examples of countries
having implemented population-based interventions
and have been successful in reducing BP and improv-
ing public health.82
ARTICLE INFORMATION
Affiliations
School of Population Health, University of New South Wales, Sydney, Austra-
lia (A.E.S.). George Institute for Global Health, Sydney, NSW, Australia (A.E.S.).
Hypertension in Africa Research Team, MRC Unit for Hypertension and Cardio-
vascular Disease, North-West University, Potchefstroom, South Africa (A.E.S.).
Centre for Chronic Conditions and Injuries, Public Health Foundation of India,
Gurgaon (N.S.V., S.M., D.P.). Centre for Chronic Disease Control, New Delhi,
India (N.S.V., S.M., D.P.). School of Exercise and Nutrition Sciences (N.S.V.) and
Faculty of Health (S.M.), Deakin University, Burwood, VIC, Australia. Depart-
ment of Epidemiology, London School of Hygiene and Tropical Medicine, United
Kingdom (D.P.).
Disclosures
None.
REFERENCES
1. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ,
Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones
DW, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/
ASPC/NMA/PCNA guideline for the prevention, detection, evalua-
tion, and management of high blood pressure in adults: a report of the
American College of Cardiology/American Heart Association Task Force
on Clinical Practice Guidelines. Hypertension. 2018;71:e13–e115. doi:
10.1161/HYP.0000000000000065
2. Institute for Health Metrics and Evaluation (IHME). Non-communica-
ble Diseases - Level 1 Cause. IHME, University of Washington, 2019.
Accessed December 16, 2020. http://www.healthdata.org/results/
gbd_summaries/2019/non-communicable-diseases-level-1-cause
3. Institute for Health Metrics and Evaluation (IHME). Cardiovascular Diseases
- Level 2 Cause. IHME, University of Washington, 2019. Accessed Decem-
ber 16, 2020. http://www.healthdata.org/results/gbd_summaries/2019/
cardiovascular-diseases-level-2-cause
4. Institute for Health Metrics and Evaluation (IHME). High Systolic
Blood Pressure - Level 2 Risk. IHME, University of Washington, 2019.
Accessed December 16, 2020. http://www.healthdata.org/results/
gbd_summaries/2019/high-systolic-blood-pressure-level-2-risk
5. Rapsomaniki E, Timmis A, George J, Pujades-Rodriguez M, Shah AD,
Denaxas S, White IR, Caulfield MJ, Deanfield JE, Smeeth L, et al. Blood
pressure and incidence of twelve cardiovascular diseases: lifetime risks,
healthy life-years lost, and age-specific associations in 1·25 million people.
Lancet. 2014;383:1899–1911. doi: 10.1016/S0140-6736(14)60685-1
6. Hsu CY, McCulloch CE, Darbinian J, Go AS, Iribarren C. Elevated
blood pressure and risk of end-stage renal disease in subjects with-
out baseline kidney disease. Arch Intern Med. 2005;165:923–928. doi:
10.1001/archinte.165.8.923
7. Walker KA, Sharrett AR, Wu A, Schneider ALC, Albert M, Lutsey PL,
Bandeen-Roche K, Coresh J, Gross AL, Windham BG, et al. Association of
midlife to late-life blood pressure patterns with incident dementia. JAMA.
2019;322:535–545. doi: 10.1001/jama.2019.10575
8. Zhou B, Bentham J, Di Cesare M; NC D Risk Factor Collaboration (NCD-RisC).
Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis
of 1479 population-based measurement studies with 19.1 million partici-
pants. Lancet. 2017;389:37–55. doi: 10.1016/S0140-6736(16)31919-5
9. Beaney T, Schutte AE, Stergiou GS, Borghi C, Burger D, Charchar F, Cro
S, Diaz A, Damasceno A, Espeche W, et al; MMM Investigators*. May Mea-
surement Month 2019: the global blood pressure screening campaign of
the International Society of Hypertension. Hypertension. 2020;76:333–341.
doi: 10.1161/HYPERTE NSIONAHA.120.14874
10. Beaney T, Schutte AE, Tomaszewski M, Ariti C, Burrell LM, Castillo RR,
Charchar FJ, Damasceno A, Kruger R, Lackland DT, et al. May Measurement
Month 2017: an analysis of blood pressure screening results worldwide.
Lancet Glob Health. 2018;6:e736–e743.
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729 April 2, 2021 823
Schutte et al Hypertension in LMICs
11. Beaney T, Burrell LM, Castillo RR, Charchar FJ, Cro S, Damasceno A, Kruger
R, Nilsson PM, Prabhakaran D, Ramirez AJ, et al; MMM Investigators. May
Measurement Month 2018: a pragmatic global screening campaign to raise
awareness of blood pressure by the International Society of Hypertension.
Eur Heart J. 2019;40:2006–2017. doi: 10.1093/eurheartj/ehz300
12. Chow CK, Teo KK, Rangarajan S, Islam S, Gupta R, Avezum A, Bahonar
A, Chifamba J, Dagenais G, Diaz R, et al; PURE (Prospective Urban
Rural Epidemiology) Study Investigators. Prevalence, awareness, treat-
ment, and control of hypertension in rural and urban communities in
high-, middle-, and low-income countries. JAMA. 2013;310:959–968. doi:
10.1001/jama.2013.184182
13. Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat
Rev Nephrol. 2020;16:223–237. doi: 10.1038/s41581-019-0244-2
14. Institute for Health Metrics and Evaluation (I HME). Summary Exposure Value.
IHME, University of Washington; 2019. Accessed December 16, 2020.
http://ghdx.healthdata.org/gbd-results-tool?params=gbd-api-2019-public
/8e7c7297c78778aea18e543bb15bee61
15. Geldsetzer P, Manne-Goehler J, Marcus ME, Ebert C, Zhumadilov Z,
Wesseh CS, Tsabedze L, Supiyev A, Sturua L, Bahendeka SK, et al. The
state of hypertension care in 44 low-income and middle-income countries:
a cross-sectional study of nationally representative individual-level data
from 1·1 million adults. Lancet. 2019;394:652–662. doi: 10.1016/S0140-
6736(19)30955-9
16. Zhao D, Qi Y, Zheng Z, Wang Y, Zhang XY, Li HJ, Liu HH, Zhang XT, Du
J, Liu J. Dietary factors associated with hypertension. Nat Rev Cardiol.
2011;8:456–465. doi: 10.1038/nrcardio.2011.75
17. Imamura F, Micha R, Khatibzadeh S, Fahimi S, Shi P, Powles J, Mozaffarian
D. Dietary quality among men and women in 187 countries in 1990 and
2010: a systematic assessment. Lancet Glob Health. 2015;3:e132–e142.
18. Hirvonen K, Bai Y, Headey D, Masters WA. Affordability of the EAT-Lancet
reference diet: a global analysis. Lancet Glob Health. 2020;8:e59–e66. doi:
10.1016/S2214-109X(19)30447-4
19. O’Donnell M, Mente A, Alderman MH, Brady AJB, Diaz R, Gupta R,
López-Jaramillo P, Luft FC, Lüscher TF, Mancia G, et al. Salt and cardiovas-
cular disease: insufficient evidence to recommend low sodium intake. Eur
Heart J. 2020;41:3363–3373. doi: 10.1093/eurheartj/ehaa586
20. He FJ, MacGregor GA. Effect of modest salt reduction on blood pressure:
a meta-analysis of randomized trials. Implications for public health. J Hum
Hypertens. 2002;16:761–770. doi: 10.1038/sj.jhh.1001459
21. Menyanu E, Russell J, Charlton K. Dietary sources of salt in low- and middle-
income countries: a systematic literature review. Int J Environ Res Public
Health. 2019;16:2082.
22. Crouch SH, Botha-Le Roux S, Delles C, Graham LA, Schutte AE. Inflam-
mation and salt in young adults: the African-PREDICT study. Eur J Nutr.
2021;60:873–882. doi: 10.1007/s00394-020-02292-3
23. Swanepoel B, Schutte AE, Cockeran M, Steyn K, Wentzel-Viljoen E. Sodium
and potassium intake in South Africa: an evaluation of 24-hour urine
collections in a white, black, and Indian population. J Am Soc Hypertens.
2016;10:829–837. doi: 10.1016/j.jash.2016.08.007
24. Hagins M, States R, Selfe T, Innes K. Effectiveness of yoga for hypertension:
systematic review and meta-analysis. Evid Based Complement Alternat Med.
2013;2013:649836. doi: 10.1155/2013/649836
25. Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran
D, Ramirez A, Schlaich M, Stergiou GS, Tomaszewski M, et al. 2020
International Society of hypertension global hypertension prac-
tice guidelines. Hypertension. 2020;75:1334–1357. doi: 10.1161/
HYPERTENSIONAHA.120.15026
26. Raghuraj P, Ramakrishnan AG, Nagendra HR, Telles S. Effect of two
selected yogic breathing techniques of heart rate variability. Indian J Physiol
Pharmacol. 1998;42:467–472.
27. The Trials of Hypertension Prevention Collaborative Research Group.
Effects of weight loss and sodium reduction intervention on blood pressure
and hypertension incidence in overweight people with high-normal blood
pressure. The Trials of Hypertension Prevention, phase II.Arch Intern Med.
1997;157:657–667. doi: 10.1001/archinte.1997.00440270105009
28. He J, Whelton PK, Appel LJ, Charleston J, Klag MJ. Long-term effects of
weight loss and dietary sodium reduction on incidence of hypertension.
Hypertension. 2000;35:544–549. doi: 10.1161/01.hyp.35.2.544
29. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D,
Obarzanek E, Conlin PR, Miller ER II I, Simons-Morton DG, et al; DASH-
Sodium Collaborative Research Group. Effects on blood pressure of
reduced dietary sodium and the Dietary Approaches to Stop Hypertension
(DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med.
2001;344:3–10. doi: 10.1056/NEJM200101043440101
30. Vollmer WM, Sacks FM, Ard J, Appel LJ, Bray GA, Simons-Morton DG, Conlin
PR, Svetkey LP, Erlinger TP, Moore TJ, et al; DASH-Sodium Trial Collaborative
Research Group. Effects of diet and sodium intake on blood pressure: sub-
group analysis of the DASH-sodium trial. Ann Intern Med. 2001;135:1019–
1028. doi: 10.7326/0003-4819-135-12-200112180-00005
31. Chobanian AV, Hill M. National Heart, Lung, and Blood Institute Workshop
on sodium and blood pressure: a critical review of current scientific evi-
dence. Hypertension. 2000;35:858–863. doi: 10.1161/01.hyp.35.4.858
32. Kelley GA, Kelley KS. Progressive resistance exercise and resting blood
pressure: a meta-analysis of randomized controlled trials. Hypertension.
2000;35:838–843. doi: 10.1161/01.hyp.35.3.838
33. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a
meta-analysis of randomized, controlled trials. Ann Intern Med. 2002;136:493–
503. doi: 10.7326/0003-4819-136-7-200204020-00006
34. Xin X, He J, Frontini MG, Ogden LG, Motsamai OI, Whelton PK. Effects of alco-
hol reduction on blood pressure: a meta-analysis of randomized controlled
trials. Hypertension. 2001;38:1112–1117. doi: 10.1161/hy1101.093424
35. World Health Organization. Tobacco Key Facts. 2020. Accessed Decem-
ber 16, 2020. https://www.who.int/news-room/fact-sheets/detail/
tobacco#:~:text=Key%20facts,exposed%20to%20second%2Dhand%20
smoke
36. Gilmore AB, Fooks G, Drope J, Bialous SA, Jackson RR. Exposing and address-
ing tobacco industry conduct in low-income and middle-income countries.
Lancet. 2015;385:1029–1043. doi: 10.1016/S0140-6736(15)60312-9
37. World Health Organization. Global Status Report on Alcohol and Health.
2018. Accessed December 16, 2020. https://www.who.int/publications/i/
item/9789241565639
38. Griswold MG, Fullman N, Hawley C; GBD 2016 Alcohol Collaborators.
Alcohol use and burden for 195 countries and territories, 1990–2016: a
systematic analysis for the Global Burden of Disease Study 2016. Lancet.
2018;392:1015-1035. doi: 10.1016/S0140-6736(18)31310-2
39. Popkin BM, Corvalan C, Grummer-Strawn LM. Dynamics of the double bur-
den of malnutrition and the changing nutrition reality. Lancet. 2020;395:65–
74. doi: 10.1016/S0140-6736(19)32497-3
40. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C,
Mullany EC, Biryukov S, Abbafati C, Abera SF, et al. Global, regional,
and national prevalence of overweight and obesity in children and
adults during 1980-2013: a systematic analysis for the Global Burden
of Disease Study 2013. Lancet. 2014;384:766–781. doi: 10.1016/
S0140-6736(14)60460-8
41. Hall JE, do Carmo JM, da Silva AA, Wang Z, Hall ME. Obesity-induced
hypertension: interaction of neurohumoral and renal mechanisms. Circ Res.
2015;116:991–1006. doi: 10.1161/CIRCRESAHA.116.305697
42. Hall ME, do Carmo JM, da Silva AA, Juncos LA, Wang Z, Hall JE. Obe-
sity, hypertension, and chronic kidney disease. Int J Nephrol Renovasc Dis.
2014;7:75–88. doi: 10.2147/IJNRD.S39739
43. Marmot M, Friel S, Bell R, Houweling TA, Taylor S; Commission on
Social Determinants of Health. Closing the gap in a generation: health
equity through action on the social determinants of health. Lancet.
2008;372:1661–1669. doi: 10.1016/S0140-6736(08)61690-6
44. Allen L, Williams J, Townsend N, Mikkelsen B, Roberts N, Foster C,
Wickramasinghe K. Socioeconomic status and non-communicable disease
behavioural risk factors in low-income and lower-middle-income coun-
tries: a systematic review. Lancet Glob Health. 2017;5:e277–e289. doi:
10.1016/S2214-109X(17)30058-X
45. Hajat A, Hsia C, O’Neill MS. Socioeconomic disparities and air pollution
exposure: a global review. Curr Environ Health Rep. 2015;2:440–450. doi:
10.1007/s40572-015-0069-5
46. World Health Organization. Global Status Report on NonCommunicable
Diseases. 2010. Accessed on December 16, 2020. https://www.who.int/
nmh/publications/ncd_report2010/
47. Kickbusch I, Allen L, Franz C. The commercial determinants of health. Lancet
Glob Health. 2016;4:e895–e896. doi: 10.1016/S2214-109X(16)30217-0
48. Ireland R, Bunn C, Reith G, Philpott M, Capewell S, Boyland E, Chambers
S. Commercial determinants of health: advertising of alcohol and unhealthy
foods during sporting events. Bull World Health Organ. 2019;97:290–295.
doi: 10.2471/BLT.18.220087
49. Marmot M, Bell R. Social determinants and non-communicable diseases:
time for integrated action. BMJ. 2019;364:l251. doi: 10.1136/bmj.l251
50. Sun L, Chen J, Li Q, Huang D. Dramatic uneven urbanization of large cities
throughout the world in recent decades. Nat Commun. 2020;11:5366. doi:
10.1038/s41467-020-19158-1
51. Anenberg SC, Achakulwisut P, Brauer M, Moran D, Apte JS, Henze
DK. Particulate matter-attributable mortality and relationships with
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
824 April 2, 2021 Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729
Schutte et al Hypertension in LMICs
carbon dioxide in 250 urban areas worldwide. Sci Rep. 2019;9:11552. doi:
10.1038/s41598-019-48057-9
52. Baumgartner J, Brauer M, Ezzati M. The role of cities in reducing the car-
diovascular impacts of environmental pollution in low- and middle-income
countries. BMC Med. 2020;18:39. doi: 10.1186/s12916-020-1499-y
53. Astell-Burt T, Feng X. Urban green space, tree canopy and prevention of
cardiometabolic diseases: a multilevel longitudinal study of 46 786 Austra-
lians. Int J Epidemiol. 2020;49:926–933. doi: 10.1093/ije/dyz239
54. Markevych I, Schoierer J, Hartig T, Chudnovsky A, Hystad P, Dzhambov
AM, de Vries S, Triguero-Mas M, Brauer M, Nieuwenhuijsen MJ, et al.
Exploring pathways linking greenspace to health: theoretical and
methodological guidance. Environ Res. 2017;158:301–317. doi:
10.1016/j.envres.2017.06.028
55. Münzel T, Sørensen M. Noise pollution and arterial hypertension. Eur Cardiol.
2017;12:26–29. doi: 10.15420/ecr.2016:31:2
56. Brook RD, Rajagopalan S, Pope CA 3rd, Brook JR, Bhatnagar A, Diez-Roux
AV, Holguin F, Hong Y, Luepker RV, Mittleman MA, et al; American Heart
Association Council on Epidemiology and Prevention, Council on the Kidney
in Cardiovascular Disease, and Council on Nutrition, Physical Activity and
Metabolism. Particulate matter air pollution and cardiovascular disease: an
update to the scientific statement from the American Heart Association.
Circulation. 2010;121:2331–2378. doi: 10.1161/CIR.0b013e3181dbece1
57. Furuyama A, Kanno S, Kobayashi T, Hirano S. Extrapulmonary translocation
of intratracheally instilled fine and ultrafine particles via direct and alveo-
lar macrophage-associated routes. Arch Toxicol. 2009;83:429–437. doi:
10.1007/s00204-008-0371-1
58. Bartoli CR, Wellenius GA, Diaz EA, Lawrence J, Coull BA, Akiyama I, Lee
LM, Okabe K, Verrier RL, Godleski JJ. Mechanisms of inhaled fine particu-
late air pollution-induced arterial blood pressure changes. Environ Health
Perspect. 2009;117:361–366. doi: 10.1289/ehp.11573
59. Prabhakaran D, Mandal S, Krishna B, Magsumbol M, Singh K, Tandon N,
Venkat Narayan KM, Shivashankar R, Kondal D, Ali MK, et al; GeoHealth
Hub Study investigators, COE-CARRS Study Investigators. Exposure to
particulate matter is associated with elevated blood pressure and inci-
dent hypertension in Urban India. Hypertension. 2020;76:1289–1298. doi:
10.1161/HYPERTE NSIONAHA.120.15373
60. Eriksson JG, Forsén TJ, Kajantie E, Osmond C, Barker DJ. Childhood growth
and hypertension in later life. Hypertension. 2007;49:1415–1421. doi:
10.1161/HYPERTE NSIONAHA.106.085597
61. Ben-Shlomo Y, McCarthy A, Hughes R, Tilling K, Davies D, Smith GD. Imme-
diate postnatal growth is associated with blood pressure in young adult-
hood: the Barry Caerphilly Growth Study. Hypertension. 2008;52:638–644.
doi: 10.1161/HYPERTE NSIONAHA.108.114256
62. Siewert-Delle A, Ljungman S. The impact of birth weight and gestational
age on blood pressure in adult life: a population-based study of 49-year-
old men. Am J Hypertens. 1998;11:946–953. doi: 10.1016/s0895-
7061(98)00090-9
63. Blencowe H, Krasevec J, de Onis M, Black RE, An X, Stevens GA, Borghi
E, Hayashi C, Estevez D, Cegolon L, et al. National, regional, and worldwide
estimates of low birthweight in 2015, with trends from 2000: a systematic
analysis. Lancet Glob Health. 2019;7:e849–e860.
64. Tauzin L, Risso F, Buffat C, Serra G, Simeoni U. Vascular mechanisms in the
developmental programming of cardio-vascular disease. Pediatr Med Chir.
2005;27:18–23.
65. Martyn CN, Barker DJ, Jespersen S, Greenwald S, Osmond C, Berry C.
Growth in utero, adult blood pressure, and arterial compliance. Br Heart J.
1995;73:116–121. doi: 10.1136/hrt.73.2.116
66. Skilton MR, Evans N, Griffiths KA, Harmer JA, Celermajer DS. Aortic
wall thickness in newborns with intrauterine growth restriction. Lancet.
2005;365:1484–1486. doi: 10.1016/S0140-6736(05)66419-7
67. Olsen MH, Angell SY, Asma S, Boutouyrie P, Burger D, Chirinos JA,
Damasceno A, Delles C, Gimenez-Roqueplo AP, Hering D, et al. A
call to action and a lifecourse strategy to address the global burden
of raised blood pressure on current and future generations: the Lan-
cet Commission on Hypertension. Lancet. 2016;388:2665–2712. doi:
10.1016/S0140-6736(16)31134-5
68. Mordi I, Mordi N, Delles C, Tzemos N. Endothelial dysfunction in human essen-
tial hypertension. J Hypertens. 2016;34:1464–1472. doi: 10.1097/HJH.
0000000000000965
69. Barker DJ, Osmond C, Forsen TJ, Kajantie E, Eriksson JG. Maternal and
social origins of hypertension. Hypertension. 2007;50:565–571. doi:
10.1161/HYPERTE NSIONAHA.107.091512
70. Mohn A, Chiavaroli V, Cerruto M, Blasetti A, Giannini C, Bucciarelli T,
Chiarelli F. Increased oxidative stress in prepubertal children born small
for gestational age. J Clin Endocrinol Metab. 2007;92:1372–1378. doi:
10.1210/jc.2006-1344
71. Franco MC, Kawamoto EM, Gorjão R, Rastelli VM, Curi R, Scavone C, Sawaya
AL, Fortes ZB, Sesso R. Biomarkers of oxidative stress and antioxidant sta-
tus in children born small for gestational age: evidence of lipid peroxidation.
Pediatr Res. 2007;62:204–208. doi: 10.1203/PDR.0b013e3180986d04
72. Drake AJ, Tang JI, Nyirenda MJ. Mechanisms underlying the role of glu-
cocorticoids in the early life programming of adult disease. Clin Sci (Lond).
2007;113:219–232. doi: 10.1042/CS20070107
73. Costantine MM, Ghulmiyyah LM, Tamayo E, Hankins GD, Saade GR, Longo
M. Transgenerational effect of fetal programming on vascular phenotype
and reactivity in endothelial nitric oxide synthase knockout mouse model.
Am J Obstet Gynecol. 2008;199:250.e1-7.
74. Lynch J, Smith GD. A life course approach to chronic disease epidemi-
ology. Annu Rev Public Health. 2005;26:1–35. doi: 10.1146/annurev.
publhealth.26.021304.144505
75. Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, Chen
J, He J. Global disparities of hypertension prevalence and control: a sys-
tematic analysis of population-based studies from 90 Countries. Circulation.
2016;134:441–450. doi: 10.1161/CIRCU LATIONAHA.115.018912
76. Kostova D, Spencer G, Moran AE, Cobb LK, Husain MJ, Datta BK,
Matsushita K, Nugent R. The cost-effectiveness of hypertension man-
agement in low-income and middle-income countries: a review. BMJ Glob
Health. 2020;5:e002213.
77. Carey RM, Muntner P, Bosworth HB, Whelton PK. Prevention and con-
trol of hypertension: JACC health promotion series. J Am Coll Cardiol.
2018;72:1278–1293. doi: 10.1016/j.jacc.2018.07.008
78. Campbell NRC, Schutte AE, Varghese CV, Ordunez P, Zhang X-H, Khan
T, Sharman JE, Whelton PK, Parati G, Weber MA, et al. Sao Paulo call to
action for the prevention and control of high blood pressure: 2020. J Clin
Hypertens. 2019;21:1744–1752.
79. Rose G. Sick individuals and sick populations. Int J Epidemiol. 1985;14:32–
38. doi: 10.1093/ije/14.1.32
80. Cobiac LJ, Tam K, Veerman L, Blakely T. Taxes and subsidies for improving
diet and population health in Australia: a cost-effectiveness modelling study.
PLoS Med. 2017;14:e1002232. doi: 10.1371/journal.pmed.1002232
81. Trieu K, Neal B, Hawkes C, Dunford E, Campbell N, Rodriguez-Fernandez
R, Legetic B, McLaren L, Barberio A, Webster J. Salt reduction initiatives
around the world - a systematic review of progress towards the global tar-
get. PLoS One. 2015;10:e0130247. doi: 10.1371/journal.pone.0130247
82. World Health Organization. High Blood Pressure - Country Experiences
and Effective Interventions Utilized Across the European Region. 2013.
Accessed February 22, 2021. https://apps.who.int/iris/bitstream/han-
dle/10665/108619/e96816.pdf?sequence=1&isAllowed=y
83. Arrúa A, Machín L, Curutchet MR, Martínez J, Antúnez L, Alcaire F, Giménez
A, Ares G. Warnings as a directive front-of-pack nutrition labelling scheme:
comparison with the Guideline Daily Amount and traffic-light systems. Public
Health Nutr. 2017;20:2308–2317. doi: 10.1017/S1368980017000866
84. World Health Organization. HEARTS Technical Package. 2018. Accessed
December 16, 2020. https://www.who.int/cardiovascular_diseases/
hearts/en/
85. NCD Risk Factor Collaboration. Worldwide trends in blood pressure from
1975 to 2015: a pooled analysis of 1479 population-based measure-
ment studies with 19.1 million participants. Lancet. 2017;389:37–55. doi:
10.1016/S0140-6736(16)31919-5
86. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier
M, Clement DL, Coca A, de Simone G, Dominiczak A, et al; Authors/
Task Force Members. 2018 ESC/ESH Guidelines for the management
of arterial hypertension: the task force for the management of arterial
hypertension of the European Society of Cardiology and the European
Society of Hypertension: the Task Force for the management of arte-
rial hypertension of the European Society of Cardiology and the Euro-
pean Society of Hypertension. J Hypertens. 2018;36:1953–2041. doi:
10.1097/HJH.0000000000001940
87. Sharman JE, O’Brien E, Alpert B, Schutte AE, Delles C, Hecht Olsen M,
Asmar R, Atkins N, Barbosa E, Calhoun D, et al; Lancet Commission on
Hypertension Group. Lancet Commission on Hypertension group posi-
tion statement on the global improvement of accuracy standards for
devices that measure blood pressure. J Hypertens. 2020;38:21–29. doi:
10.1097/HJH.0000000000002246
88. World Health Organization. WHO Technical Specifications for Automated
Non-Invasive Blood Pressure Measuring Devices With Cuff. 2020. Accessed
December 16, 2020. https://www.who.int/medical_devices/publications/
tech_specs_automated_non_invasive_blood_pressure_with_cuff/en/
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729 April 2, 2021 825
Schutte et al Hypertension in LMICs
89. World Health Organization. Fourth WHO Global Forum on Medical Devices
Report. 2019. Accessed December 16, 2020. https://www.who.int/
medical_devices/global_forum/4th_gfmd/en/
90. Padwal R, Campbell NRC, Schutte AE, Olsen MH, Delles C, Etyang A,
Cruickshank JK, Stergiou G, Rakotz MK, Wozniak G, et al. Optimizing ob-
server performance of clinic blood pressure measurement: a position state-
ment from the Lancet Commission on Hypertension Group. J Hypertens.
2019;37:1737–1745. doi: 10.1097/HJH.0000000000002112
91. Odili AN, Abdullahi B, Nwankwo AM, Asayama K, Staessen JA.
Characteristics of self-measured home blood pressure in a Nigerian urban
community: the NIPR EGH study. Blood Press Monit. 2015;20:260–265.
doi: 10.1097/MBP.0000000000000136
92. He J, Irazola V, Mills KT, Poggio R, Beratarrechea A, Dolan J, Chen CS,
Gibbons L, Krousel-Wood M, Bazzano LA, et al; HCPIA Investigators. Effect
of a community health worker-led multicomponent intervention on blood
pressure control in low-income patients in Argentina: a randomized clinical
trial. JAMA. 2017;318:1016–1025. doi: 10.1001/jama.2017.11358
93. Piette JD, Datwani H, Gaudioso S, Foster SM, Westphal J, Perry W,
Rodríguez-Saldaña J, Mendoza-Avelares MO, Marinec N. Hypertension
management using mobile technology and home blood pressure moni-
toring: results of a randomized trial in two low/middle-income countries.
Telemed J E Health. 2012;18:613–620. doi: 10.1089/tmj.2011.0271
94. Burger R, Christian CS, Gerdtham UG, Haal K, Hompashe DM, Smith
A, Schutte AE. Use of simulated patients to assess hypertension case
management at public healthcare facilities in South Africa. J Hypertens.
2020;38:362–367. doi: 10.1097/HJH.0000000000002258
95. World Health Organization. Physical Activity Fact Sheet. 2020. Accessed
December 16, 2020. https://www.who.int/news-room/fact-sheets/detail/
physical-activity
96. Turnbull F; Blood Pressure Lowering Treatment Trialists’ Collaboration.
Effects of different blood-pressure-lowering regimens on major cardiovascu-
lar events: results of prospectively-designed overviews of randomised trials.
Lancet. 2003;362:1527–1535. doi: 10.1016/s0140-6736(03)14739-3
97. Attaei MW, Khatib R, McKee M, Lear S, Dagenais G, Igumbor EU, AlHabib
KF, Kaur M, Kruger L, Teo K, et al; PURE Study Investigators. Availability
and affordability of blood pressure-lowering medicines and the effect on
blood pressure control in high-income, middle-income, and low-income
countries: an analysis of the PURE study data. Lancet Public Health.
2017;2:e411–e419. doi: 10.1016/S2468-2667(17)30141-X
98. Benjamin IJ, Kreutz R, Olsen MH, Schutte AE, Lopez-Jaramillo P, Frieden
TR, Sliwa K, Lackland DT, Brainin M. Fixed-dose combination antihy-
pertensive medications. Lancet. 2019;394:637–638. doi: 10.1016/
S0140-6736(19)31629-0
99. Wang N, Salam A, Webster R, de Silva A, Guggilla R, Stepien S, Mysore
J, Billot L, Jan S, Maulik PK, et al; TRIU MPH Study Group. Association
of low-dose triple combination therapy with therapeutic inertia and
prescribing patterns in patients with hypertension: a secondary analy-
sis of the TRIUMPH trial. JAMA Cardiol. 2020;5:1219–1226. doi:
10.1001/jamacardio.2020.2739
100. Webster R, Salam A, de Silva HA, Selak V, Stepien S, Rajapakse S,
Amarasekara S, Amarasena N, Billot L, de Silva AP, et al; TRIUMPH Study
Group. Fixed low-dose triple combination antihypertensive medication vs
usual care for blood pressure control in patients with mild to moderate hy-
pertension in Sri Lanka: a randomized clinical trial. JAMA. 2018;320:566–
579. doi: 10.1001/jama.2018.10359
101. Yusuf S, Joseph P, Dans A, Gao P, Teo K, Xavier D, López-Jaramillo P, Yusoff
K, Santoso A, Gamra H, et al; International Polycap Study 3 Investigators.
Polypill with or without aspirin in persons without cardiovascular disease. N
Engl J Med. 2021;384:216–228. doi: 10.1056/NEJ Moa2028220
102. U.S. Department of Health and Human Services. The Surgeon General’s
Call to Action to Control Hypertension. 2020. Accessed November 30,
2020. https://www.hhs.gov/sites/default/files/call-to-action-to-control-
hypertension.pdf
103. Rea F, Corrao G, Merlino L, Mancia G. Initial antihypertensive treatment
strategies and therapeutic inertia. Hypertension. 2018;72:846–853. doi:
10.1161/HYPERTE NSIONAHA.118.11308
104. van der Linden EL, Agyemang C, van den Born BH. Hypertension control
in sub-Saharan Africa: clinical inertia is another elephant in the room. J Clin
Hypertens (Greenwich). 2020;22:959–961. doi: 10.1111/jch.13874
105. World Health Organization. Adherence to Long-Term Therapies: Evidence
for Action. 2003. Accessed December 16, 2020. https://www.who.int/
chp/knowledge/publications/adherence_full_report.pdf?ua=1
106. Morisky DE, Ang A, Krousel-Wood M, Ward HJ. Predictive validity of a
medication adherence measure in an outpatient setting. J Clin Hypertens
(Greenwich). 2008;10:348–354. doi: 10.1111/j.1751-7176.2008.07572.x
107. Kim MT, Hill MN, Bone LR, Levine DM. Development and testing of the Hill-
Bone compliance to high blood pressure therapy scale. Prog Cardiovasc
Nurs. 2000;15:90–96. doi: 10.1111/j.1751-7117.2000.tb00211.x
108. Chen SL, Tsai JC, Lee WL. The impact of illness perception on adherence
to therapeutic regimens of patients with hypertension in Taiwan. J Clin
Nurs. 2009;18:2234–2244. doi: 10.1111/j.1365-2702.2008.02706.x
109. Modesti PA, Wang J, Damasceno A, Agyemang C, Van Bortel L, Persu
A, Zhao D, Jarraya F, Marzotti I, Bamoshmoosh M, et al. Indirect implica-
tions of COVID-19 prevention strategies on non-communicable diseases:
an opinion paper of the European Society of Hypertension working group
on hypertension and cardiovascular risk assessment in subjects living in
or emigrating from low resource settings. BMC Med. 2020;18:256. doi:
10.1186/s12916-020-01723-6
110. Nielsen JØ, Shrestha AD, Neupane D, Kallestrup P. Non-adherence to
anti-hypertensive medication in low- and middle-income countries: a sys-
tematic review and meta-analysis of 92443 subjects. J Hum Hypertens.
2017;31:14–21. doi: 10.1038/jhh.2016.31
111. Macquart de Terline D, Kane A, Kramoh KE, et al. Factors associ-
ated with poor adherence to medication among hypertensive patients
in twelve low and middle income Sub-Saharan countries. PLoS One.
2019;14:e0219266.
112. Burnier M, Egan BM. Adherence in hypertension. Circ Res. 2019;124:1124–
1140. doi: 10.1161/CIRCRESAHA.118.313220
113. GBD 2019 Risk Factors Collaborators. Global burden of 87 risk factors
in 204 countries and territories, 1990-2019: a systematic analysis for the
Global Burden of Disease Study 2019. Lancet. 2020;396:1223-1249. doi:
10.1016/S0140-6736(20)30752-2
114. European Society of Hypertension Corona-virus Disease 19 Task Force*
The corona-virus disease 2019 pandemic compromised routine care
for hypertension: a survey conducted among excellence centers of the
European Society of Hypertension. J Hypertens. 2021;39:190–195. doi:
10.1097/HJH.0000000000002703
115. Skeete J, Connell K, Ordunez P, DiPette DJ. Approaches to the manage-
ment of hypertension in resource-limited settings: strategies to overcome
the hypertension crisis in the Post-COVID Era. Integr Blood Press Control.
2020;13:125–133. doi: 10.2147/IBPC.S261031
116. The World Bank. Physicians (per 1,000 people) - India, Japan, Nigeria,
Mozambique. The World Bank, 2020. Accessed December 14, 2020.
https://data.worldbank.org/indicator/SH.MED.PHYS.ZS?end=
2018&locations=IN-JP-NG-M Z&start=1960&view=c
hart&year=1999
117. The World Bank. Nurses and midwives (per 1,000 people) - India, Japan,
Nigeria, Mozambique. The World Bank, 2020. Accessed December
14, 2020. https://data.worldbank.org/indicator/SH.MED.N UMW.
P3?end=2018&locations=IN-JP-NG-M Z&start=1960&view=
chart&year=1999
118. World Health Organization. Health Workforce. 2020. Accessed December 16,
2020. https://www.who.int/health-topics/health-workforce#tab=tab_2
119. World Health Organization. Working for Health and Growth: Investing in
the Health Workforce. Report of the High-Level Commission on Health
Employment and Economic Growth. 2016. Accessed December 16,
2020. https://apps.who.int/iris/bitstream/handle/10665/250047/
9789241511308-eng.pdf?sequence=1
120. Ataklte F, Erqou S, Kaptoge S, Taye B, Echouffo-Tcheugui JB, Kengne
AP. Burden of undiagnosed hypertension in sub-saharan Africa: a sys-
tematic review and meta-analysis. Hypertension. 2015;65:291–298. doi:
10.1161/HYPERTE NSIONAHA.114.04394
121. Lozano R, Fullman N, Mumford JE; GBD 2019 Universal Health Coverage
Collaborators. Measuring universal health coverage based on an index of ef-
fective coverage of health services in 204 countries and territories, 1990–
2019: a systematic analysis for the Global Burden of Disease Study 2019.
Lancet. 2020;396:1250–1284. doi: 10.1016/S0140-6736(20)30750-9
122. Frieden TR, Varghese CV, Kishore SP, Campbell NRC, Moran AE, Padwal R,
Jaffe MG. Scaling up effective treatment of hypertension-A pathfinder for
universal health coverage. J Clin Hypertens (Greenwich). 2019;21:1442–
1449. doi: 10.1111/jch.13655
123. Wagstaff A, Flores G, Hsu J, Smitz MF, Chepynoga K, Buisman LR,
van Wilgenburg K, Eozenou P. Progress on catastrophic health spending
in 133 countries: a retrospective observational study. Lancet Glob Health.
2018;6:e169–e179. doi: 10.1016/S2214-109X(17)30429-1
124. Brinda EM, Andrés AR, Andrés RA, Enemark U. Correlates of out-of-
pocket and catastrophic health expenditures in Tanzania: results from a
national household survey. BMC Int Health Hum Rights. 2014;14:5. doi:
10.1186/1472-698X-14-5
Downloaded from http://ahajournals.org by on April 1, 2021

HYPERTENSION COMPENDIUM
826 April 2, 2021 Circulation Research. 2021;128:808–826. DOI: 10.1161/CIRCRESAHA.120.318729
Schutte et al Hypertension in LMICs
125. Pandey A, Ploubidis GB, Clarke L, Dandona L. Trends in catastrophic health
expenditure in India: 1993 to 2014. Bull World Health Organ. 2018;96:18–
28. doi: 10.2471/BLT.17.191759
126. Murphy A, Palafox B, Walli-Attaei M, Powell-Jackson T, Rangarajan S, Alhabib
KF, Avezum AJ, Calik KBT, Chifamba J, Choudhury T, et al. The household
economic burden of non-communicable diseases in 18 countries. BMJ
Glob Health. 2020;5:e002040. doi: 10.1136/bmjgh-2019-002040
127. Londoño Agudelo E, García Fariñas A, Pérez Ospina V, Taborda Pérez C,
Villacrés Landeta T, Battaglioli T, Gómez Arias R, Van der Stuyft P. Out-of-
pocket expenditure for hypertension care: a population-based study in low-
income urban Medellin, Colombia. Glob Health Action. 2020;13:1806527.
doi: 10.1080/16549716.2020.1806527
128. World Health Organization. Out-of-Pocket Payments, User Fees and
Catastrophic Expenditure. 2020. Accessed December 16, 2020.
https://www.who.int/health_financing/topics/financial-protection/
out-of-pocket-payments/en/
129. World Health Organization. mHealth: New Horizons for Health Through
Mobile Technologies: Second Global Survey on eHealth. 2011.
Accessed December 16, 2020. https://apps.who.int/iris/bitstream/han-
dle/10665/44607/9789241564250_eng.pdf?sequence=1&isAllowed=y
130. Bahia K, Suardi S. The State of Mobile Internet Connectivity. 2020.
Accessed November 29, 2020. https://www.gsma.com/r/wp-content/
uploads/2020/09/GSMA-State-of-Mobile-Internet-Connectivity-
Report-2020.pdf
131. Vedanthan R, Bernabe-Ortiz A, Herasme OI, Joshi R, Lopez-Jaramillo P,
Thrift AG, Webster J, Webster R, Yeates K, Gyamfi J, et al. Innovative ap-
proaches to hypertension control in low- and middle-income countries.
Cardiol Clin. 2017;35:99–115. doi: 10.1016/j.ccl.2016.08.010
132. Weber MA, Lackland DT. The new wave of Asia: a major step for-
ward in confronting global hypertension. J Clin Hypertens (Greenwich).
2020;22:317–318. doi: 10.1111/jch.13801
133. Mao Y, Lin W, Wen J, Chen G. Impact and efficacy of mobile health inter-
vention in the management of diabetes and hypertension: a systematic
review and meta-analysis. BMJ Open Diabetes Res Care. 2020;8:e001225.
134. Prabhakaran D, Jha D, Ajay VS, Roy A, Perel P. Response by
Prabhakaran et al to Letter Regarding Article, “Effectiveness of an
mHealth-based electronic decision support system for integrated
management of chronic conditions in primary care: the mWellcare
Cluster-Randomized Controlled Trial”. Circulation. 2019;139:e1039. doi:
10.1161/CIRCU LATIONAHA.119.040782
135. Anchala R, Kaptoge S, Pant H, Di Angelantonio E, Franco OH, Prabhakaran
D. Evaluation of effectiveness and cost-effectiveness of a clinical decision
support system in managing hypertension in resource constrained primary
health care settings: results from a cluster randomized trial. J Am Heart
Assoc. 2015;4:e001213. doi: 10.1161/JAHA.114.001213
136. Tian M, Ajay VS, Dunzhu D, Hameed SS, Li X, Liu Z, Li C, Chen H, Cho K,
Li R, et al. A cluster-randomized, controlled trial of a simplified multifaceted
management program for individuals at high cardiovascular risk (SimCard
Trial) in Rural Tibet, China, and Haryana, India. Circulation. 2015;132:815–
824. doi: 10.1161/CIRCU LATIONAHA.115.015373
137. World Health Organization. Task Shifting: Rational Redistribution of
Tasks among Health Workforce Teams: Global Recommendations and
Guidelines. 2008. Accessed December 16, 2020. https://apps.who.int/
iris/bitstream/handle/10665/43821/9789241596312_eng.pdf?seque
nce=1&isAllowed=y
138. Samb B, Celletti F, Holloway J, Van Damme W, De Cock KM, Dybul M.
Rapid expansion of the health workforce in response to the HIV epidemic.
N Engl J Med. 2007;357:2510–2514. doi: 10.1056/NEJMsb071889
139. Callaghan M, Ford N, Schneider H. A systematic review of task- shifting
for HIV treatment and care in Africa. Hum Resour Health. 2010;8:8. doi:
10.1186/1478-4491-8-8
140. Huicho L, Scherpbier RW, Nkowane AM, Victora CG; Multi-Country
Evaluation of IMCI Study Group. How much does quality of child care vary
between health workers with differing durations of training? An observation-
al multicountry study. Lancet. 2008;372:910–916. doi: 10.1016/S0140-
6736(08)61401-4
141. Christopher JB, Le May A, Lewin S, Ross DA. Thirty years after Alma-Ata:
a systematic review of the impact of community health workers deliver-
ing curative interventions against malaria, pneumonia and diarrhoea on
child mortality and morbidity in sub-Saharan Africa. Hum Resour Health.
2011;9:27. doi: 10.1186/1478-4491-9-27
142. Lewin S, Munabi-Babigumira S, Glenton C, Daniels K, Bosch-Capblanch X,
van Wyk BE, Odgaard-Jensen J, Johansen M, Aja GN, Zwarenstein M, et
al. Lay health workers in primary and community health care for maternal
and child health and the management of infectious diseases. Cochrane
Database Syst Rev. 2010:CD004015.
143. Seidman G, Atun R. Does task shifting yield cost savings and improve ef-
ficiency for health systems? A systematic review of evidence from low-
income and middle-income countries. Hum Resour Health. 2017;15:29.
doi: 10.1186/s12960-017-0200-9
144. Joshi R, Alim M, Kengne AP, Jan S, Maulik PK, Peiris D, Patel AA. Task
shifting for non-communicable disease management in low and middle
income countries–a systematic review. PLoS One. 2014;9:e103754. doi:
10.1371/journal.pone.0103754
145. Gaziano TA, Abrahams-Gessel S, Denman CA, Montano CM, Khanam M,
Puoane T, Levitt NS. An assessment of community health workers’ abil-
ity to screen for cardiovascular disease risk with a simple, non-invasive
risk assessment instrument in Bangladesh, Guatemala, Mexico, and South
Africa: an observational study. Lancet Glob Health. 2015;3:e556–e563.
doi: 10.1016/S2214-109X(15)00143-6
146. Anand TN, Joseph LM, Geetha AV, Prabhakaran D, Jeemon P. Task shar-
ing with non-physician health-care workers for management of blood
pressure in low-income and middle-income countries: a systematic re-
view and meta-analysis. Lancet Glob Health. 2019;7:e761–e771. doi:
10.1016/S2214-109X(19)30077-4
147. Ojji DB, Mayosi B, Francis V, Badri M, Cornelius V, Smythe W, Kramer N,
Barasa F, Damasceno A, Dzudie A, et al; CREOLE Study Investigators.
Comparison of dual therapies for lowering blood pressure in black Africans.
N Engl J Med. 2019;380:2429–2439. doi: 10.1056/N EJMoa1901113
148. Ali MK, Chwastiak L, Poongothai S, Emmert-Fees KMF, Patel SA, Anjana
RM, Sagar R, Shankar R, Sridhar GR, Kosuri M, et al; IN DEPENDENT
Study Group. Effect of a collaborative care model on depressive
symptoms and glycated hemoglobin, blood pressure, and serum cho-
lesterol among patients with depression and diabetes in India: the
INDE PENDENT randomized clinical trial. JAMA. 2020;324:651–662. doi:
10.1001/jama.2020.11747
149. Ajay VS, Jindal D, Roy A, Venugopal V, Sharma R, Pawar A, Kinra S, Tandon
N, Prabhakaran D. Development of a smartphone-enabled hypertension
and diabetes mellitus management package to facilitate evidence-based
care delivery in primary healthcare facilities in India: the mPower heart proj-
ect. J Am Heart Assoc. 2016;5:e004343.
150. Patel SA, Dhillon PK, Kondal D, Jeemon P, Kahol K, Manimunda SP,
Purty AJ, Deshpande A, Negi PC, Ladhani S, et al. Chronic disease con-
cordance within Indian households: a cross-sectional study. PLoS Med.
2017;14:e1002395. doi: 10.1371/journal.pmed.1002395
151. Shen Y, Peng X, Wang M, Zheng X, Xu G, Lü L, Xu K, Burstrom B,
Burstrom K, Wang J. Family member-based supervision of patients with
hypertension: a cluster randomized trial in rural China. J Hum Hypertens.
2017;31:29–36. doi: 10.1038/jhh.2016.8
152. Global Alliance for Chronic Disease. 2021. Accessed February 22, 2021.
https://www.gacd.org/
153. National Institutes of Health. Fogarty International Centre. 2021. Accessed
February 22, 2021. https://www.fic.nih.gov/
154. Wellcome Trust. 2021. Accessed February 22, 2021. https://wellcome.
org/
155. National Institute for Health Research. 2021. Accessed on February 22,
2021. https://www.nihr.ac.uk/
156. National Health and Medical Research Council. 2021. Accessed on
February 22, 2021. https://www.nhmrc.gov.au
157. India Alliance DBT Wellcome. 2021. Accessed on February 22, 2021.
https://www.indiaalliance.org/
158. South African Medical Research Council. 2021. Accessed on February 22,
2021. https://www.samrc.ac.za/
159. Links. 2021. Accessed on February 22, 2021. https://linkscommunity.org/
160. National Institutes of Health and Fogarty International Centre. Global
Environmental and Occupational Health (GEOHealth). 2021. Accessed
February 22, 2021. https://www.fic.nih.gov/Programs/Pages/environ-
mental-occupational.aspx
161. Aifah A, Iwelunmor J, Akwanalo C, Allison J, Amberbir A, Asante KP,
Baumann A, Brown A, Butler M, Dalton M, et al. The Kathmandu declara-
tion on global CVD/Hypertension research and implementation science:
a framework to advance implementation research for cardiovascular and
other noncommunicable diseases in low- and middle-income Countries.
Glob Heart. 2019;14:103–107. doi: 10.1016/j.gheart.2019.05.006
162. World Health Organization. Scaling Up Action Against Noncommunicable
Diseases: How Much will it Cost? 2011. Accessed February 22, 2021. https://
apps.who.int/iris/bitstream/handle/10665/44706/9789241502313_
eng.pdf;jsessionid=5E6994E058684E512D3874D45CA75256?
sequence=1
Downloaded from http://ahajournals.org by on April 1, 2021